Advertisement

Protein Folding: An Introduction

  • Cláudio M. GomesEmail author
  • Patrícia F. N. FaíscaEmail author
Chapter
Part of the SpringerBriefs in Molecular Science book series (BRIEFSMOLECULAR)

Abstract

We have come a long way since coining of the term protein and the early findings that proteins are charged macromolecules composed of strings of amino acids linked by peptide bonds. Today, structural biologists have technologies that allow in many cases to achieve an atomic-level understanding of protein structure, dynamics and folding; protein physics approaches have made substantial contributions to understanding the intricacies of folding mechanisms and its energetics; biochemists have developed conceptual frameworks to relate protein structure with biological functions. Yet, despite the efforts of a vibrant community of protein scientists, a lot of questions remain to be answered in the field of protein structure and folding.

References

  1. 1.
    Tanford C, Reynolds J (2001) Nature’s robots—a history of proteins. OxfordGoogle Scholar
  2. 2.
    Anson ML, Mirsky AE (1930) The reversibility of protein coagulation. J Phys Chem 35:185–193Google Scholar
  3. 3.
    Astbury WT, Woods HJ (1930) The X-ray interpretation of the structure and elastic properties of hair keratin. Nature 126:913Google Scholar
  4. 4.
    Cohen C (1998) Why fibrous proteins are romantic. J Struct Biol 122:3–16PubMedGoogle Scholar
  5. 5.
    Eisenberg D (2003) The discovery of the α-helix and β-sheet, the principal structural features of proteins. Proc Natl Acad Sci 100:11207–11210PubMedGoogle Scholar
  6. 6.
    Strandberg B (2009) Building the ground for the first two protein structures: myoglobin and haemoglobin (Chap. 1). J Mol Biol 392:2–10Google Scholar
  7. 7.
    Dill KA, MacCallum JL (2012) The protein-folding problem, 50 years on. Science 338:1042–1046PubMedGoogle Scholar
  8. 8.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242PubMedPubMedCentralGoogle Scholar
  9. 9.
    Hou J, Sims GE, Zhang C, Kim S-H (2003) A global representation of the protein fold space. Proc Natl Acad Sci 100:2386–2390PubMedGoogle Scholar
  10. 10.
    Schaeffer RD, Daggett V (2011) Protein folds and protein folding. Protein Eng Des Sel PEDS 24:11–19PubMedGoogle Scholar
  11. 11.
    Richardson JS (1977) [beta]-Sheet topology and the relatedness of proteins. Nature 268:495–500PubMedGoogle Scholar
  12. 12.
    Mansfield ML (1994) Are there knots in proteins? Nat Struct Mol Biol 1:213–214Google Scholar
  13. 13.
    Taylor WR (2000) A deeply knotted protein structure and how it might fold. Nature 406:916–919PubMedGoogle Scholar
  14. 14.
    Koniaris K, Muthukumar M (1991) Knottedness in ring polymers. Phys Rev Lett 66:2211–2214PubMedGoogle Scholar
  15. 15.
    Bölinger D, Sułkowska JI, Hsu H-P, Mirny LA, Kardar M, Onuchic JN, Virnau P (2010) A Stevedore’s protein knot. PLoS Comput Biol 6:e1000731PubMedPubMedCentralGoogle Scholar
  16. 16.
    King NP, Yeates EO, Yeates TO (2007) Identification of rare slipknots in proteins and their implications for stability and folding. J Mol Biol 373:153–166PubMedGoogle Scholar
  17. 17.
    Jamroz M, Niemyska W, Rawdon EJ, Stasiak A, Millett KC, Sułkowski P, Sulkowska JI (2015) KnotProt: a database of proteins with knots and slipknots. Nucleic Acids Res 43:D306–D314PubMedGoogle Scholar
  18. 18.
    Lua RC, Grosberg AY (2006) Statistics of knots, geometry of conformations, and evolution of proteins. PLoS Comput Biol 2:e45PubMedPubMedCentralGoogle Scholar
  19. 19.
    Virnau P, Mirny LA, Kardar M (2006) Intricate knots in proteins: function and evolution. PLoS Comput Biol 2:e122PubMedPubMedCentralGoogle Scholar
  20. 20.
    Sułkowska JI, Rawdon EJ, Millett KC, Onuchic JN, Stasiak A (2012) Conservation of complex knotting and slipknotting patterns in proteins. Proc Natl Acad Sci 109:E1715–E1723PubMedGoogle Scholar
  21. 21.
    Soler MA, Nunes A, Faísca PFN (2014) Effects of knot type in the folding of topologically complex lattice proteins. J Chem Phys 141:025101PubMedGoogle Scholar
  22. 22.
    Nureki O, Shirouzu M, Hashimoto K, Ishitani R, Terada T, Tamakoshi M, Oshima T, Chijimatsu M, Takio K, Vassylyev DG, Shibata T, Inoue Y, Kuramitsu S, Yokoyama S (2002) An enzyme with a deep trefoil knot for the active-site architecture. Acta Crystallogr Sect D 58:1129–1137Google Scholar
  23. 23.
    Jacobs SA, Harp JM, Devarakonda S, Kim Y, Rastinejad F, Khorasanizadeh S (2002) The active site of the SET domain is constructed on a knot. Nat Struct Mol Biol 9:833–838Google Scholar
  24. 24.
    Sułkowska JI, Sułkowski P, Szymczak P, Cieplak M (2008) Stabilizing effect of knots on proteins. Proc Natl Acad Sci 105:19714–19719PubMedGoogle Scholar
  25. 25.
    Alam MT, Yamada T, Carlsson U, Ikai A (2002) The importance of being knotted: effects of the C-terminal knot structure on enzymatic and mechanical properties of bovine carbonic anhydrase II 1. FEBS Lett 519:35–40PubMedGoogle Scholar
  26. 26.
    Soler MA, Faísca PFN (2013) Effects of knots on protein folding properties. PLoS ONE 8:e74755PubMedPubMedCentralGoogle Scholar
  27. 27.
    Uversky VN (2014) Intrinsically disordered proteins. Springer, New YorkGoogle Scholar
  28. 28.
    Theillet FX, Binolfi A, Frembgen-Kesner T, Hingorani K, Sarkar M, Kyne C, Li C, Crowley PB, Gierasch L, Pielak GJ, Elcock AH, Gershenson A, Selenko P (2014) Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs). Chem Rev 114:6661–6714PubMedPubMedCentralGoogle Scholar
  29. 29.
    Riback JA, Bowman MA, Zmyslowski AM, Knoverek CR, Jumper JM, Hinshaw JR, Kaye EB, Freed KF, Clark PL, Sosnick TR (2017) Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water. Science 358:238–241PubMedPubMedCentralGoogle Scholar
  30. 30.
    van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, Fuxreiter M, Gough J, Gsponer J, Jones DT, Kim PM, Kriwacki RW, Oldfield CJ, Pappu RV, Tompa P, Uversky VN, Wright PE, Babu MM (2014) Classification of intrinsically disordered regions and proteins. Chem Rev 114:6589–6631PubMedPubMedCentralGoogle Scholar
  31. 31.
    Kumar S, Nussinov R (2002) Close-range electrostatic interactions in proteins. Chembiochem Eur J Chem Biol 3:604–617Google Scholar
  32. 32.
    Kessel A, Ben-Tal N (2011) Introduction to proteins: structure, function, and motion. CRC; London: Taylor & Francis [distributor], Boca RatonGoogle Scholar
  33. 33.
    Williamson MP (2012) How proteins work. Garland science, London: Taylor & Francis [distributor], New YorkGoogle Scholar
  34. 34.
    Gomes CM, Wittung-Stafshede P (2011) Protein folding and metal ions: mechanisms, biology and disease. CRC Press, Boca RatonGoogle Scholar
  35. 35.
    Gomes CM (2012) Protein misfolding in disease and small molecule therapies. Curr Top Med Chem 12:2460–2469PubMedGoogle Scholar
  36. 36.
    Leandro P, Gomes CM (2008) Protein misfolding in conformational disorders: rescue of folding defects and chemical chaperoning. Mini Rev Med Chem 8:901–911PubMedGoogle Scholar
  37. 37.
    Anfinsen CB, Haber E, Sela M, White FH Jr (1961) The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc Natl Acad Sci USA 47:1309–1314PubMedGoogle Scholar
  38. 38.
    Anfinsen CB, Sela M, Cooke JP (1962) The reversible reduction of disulphide bonds in polyalanyl ribonuclease. J Biol Chem 237:1825–1831PubMedGoogle Scholar
  39. 39.
    Sela M, Anfinsen CB (1957) Some spectrophotometric and polarimetric experiments with ribonuclease. Biochem Biophys Acta 24:229–235PubMedGoogle Scholar
  40. 40.
    Sela M, Anfinsen CB, Harrington WF (1957) The correlation of ribonuclease activity with specific aspects of tertiary structure. Biochem Biophys Acta 26:502–512PubMedGoogle Scholar
  41. 41.
    Sela M, White FH Jr, Anfinsen CB (1957) Reductive cleavage of disulphide bridges in ribonuclease. Science 125:691–692PubMedGoogle Scholar
  42. 42.
    Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181:223–230PubMedGoogle Scholar
  43. 43.
    Pace CN, Shaw KL (2000) Linear extrapolation method of analyzing solvent denaturation curves. Proteins Suppl 4:1–7Google Scholar
  44. 44.
    Shaw KL, Scholtz JM, Pace CN, Grimsley GR (2009) Determining the conformational stability of a protein using urea denaturation curves. Methods Mol Biol 490:41–55Google Scholar
  45. 45.
    Johnson CM (2013) Differential scanning calorimetry as a tool for protein folding and stability. Arch Biochem Biophys 531:100–109PubMedGoogle Scholar
  46. 46.
    Taverna DM, Goldstein RA (2002) Why are proteins marginally stable? Proteins 46:105–109PubMedGoogle Scholar
  47. 47.
    Stetter KO (1996) Hyperthermophilic procaryotes. FEMS Microbiol Rev 18:149–158Google Scholar
  48. 48.
    Madigan MT, Orent A (1999) Thermophilic and halophilic extremophiles. Curr Opin Microbiol 2:265–269PubMedGoogle Scholar
  49. 49.
    Empadinhas N, da Costa MS (2006) Diversity and biosynthesis of compatible solutes in hyper/thermophiles. Int Microbiol Off J Span Soc Microbiol 9:199–206Google Scholar
  50. 50.
    Mehta R, Singhal P, Singh H, Damle D, Sharma AK (2016) Insight into thermophiles and their wide-spectrum applications. 3 Biotech 6:81–81Google Scholar
  51. 51.
    Marx V (2016) PCR: the price of infidelity. Nat Meth 13:475–479Google Scholar
  52. 52.
    Bult CJ, White O, Olsen GJ, Zhou L, Fleischmann RD, Sutton GG, Blake JA, FitzGerald LM, Clayton RA, Gocayne JD, Kerlavage AR, Dougherty BA, Tomb J-F, Adams MD, Reich CI, Overbeek R, Kirkness EF, Weinstock KG, Merrick JM, Glodek A, Scott JL, Geoghagen NSM, Weidman JF, Fuhrmann JL, Nguyen D, Utterback TR, Kelley JM, Peterson JD, Sadow PW, Hanna MC, Cotton MD, Roberts KM, Hurst MA, Kaine BP, Borodovsky M, Klenk H-P, Fraser CM, Smith HO, Woese CR, Venter JC (1996) Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science 273:1058PubMedGoogle Scholar
  53. 53.
    Land M, Hauser L, Jun S-R, Nookaew I, Leuze MR, Ahn T-H, Karpinets T, Lund O, Kora G, Wassenaar T, Poudel S, Ussery DW (2015) Insights from 20 years of bacterial genome sequencing. Funct Integr Genomics 15:141–161PubMedPubMedCentralGoogle Scholar
  54. 54.
    Radestock S, Gohlke H (2011) Protein rigidity and thermophilic adaptation. Proteins 79:1089–1108PubMedGoogle Scholar
  55. 55.
    Scandurra R, Consalvi V, Chiaraluce R, Politi L, Engel PC (2000) Protein stability in extremophilic archaea. Front Biosci J Virtual Libr 5:D787–D795Google Scholar
  56. 56.
    Siddiqui KS (2017) Defying the activity-stability trade-off in enzymes: taking advantage of entropy to enhance activity and thermostability. Crit Rev Biotechnol 37:309–322PubMedGoogle Scholar
  57. 57.
    Anson ML (1945) Protein denaturation and the properties of protein groups. Adv Protein Chem 2:361–386Google Scholar
  58. 58.
    Chan HS, Shimizu S, Kaya H (2004) Cooperativity principles in protein folding. Methods Enzymol 380:350–379PubMedGoogle Scholar
  59. 59.
    Ptitsyn OB (1995) Molten globule and protein folding. Adv Protein Chem 47:83–229PubMedGoogle Scholar
  60. 60.
    Ptitsyn OB (1995) How the molten globule became. Trends Biochem Sci 20:376–379PubMedGoogle Scholar
  61. 61.
    Lumry R, Biltonen R, Brandts JF (1966) Validity of the “two-state” hypothesis for conformational transitions of proteins. Biopolymers 4:917–944PubMedGoogle Scholar
  62. 62.
    Fersht A (1999) Structure and mechanism in protein science: a guide to enzyme catalysis and protein folding. Freeman, W. HGoogle Scholar
  63. 63.
    Chan HS, Zhang Z, Wallin S, Liu Z (2011) Cooperativity, local-nonlocal coupling, and nonnative interactions: principles of protein folding from coarse-grained models. Annu Rev Phys Chem 62:301–326PubMedGoogle Scholar
  64. 64.
    Krishna MMG, Englander SW (2005) The N-terminal to C-terminal motif in protein folding and function. Proc Natl Acad Sci USA 102:1053–1058PubMedGoogle Scholar
  65. 65.
    Krobath H, Rey A, Faisca PFN (2015) How determinant is N-terminal to C-terminal coupling for protein folding? Phys Chem Chem Phys 17:3512–3524PubMedGoogle Scholar
  66. 66.
    Krobath H, Estácio SG, Faísca PFN, Shakhnovich EI (2012) Identification of a conserved aggregation-prone intermediate state in the folding pathways of Spc-SH3 amyloidogenic variants. J Mol Biol 422:705–722PubMedGoogle Scholar
  67. 67.
    Loureiro RJS, Vila-Viçosa D, Machuqueiro M, Shakhnovich EI, Faísca PFN (2017) A tale of two tails: the importance of unstructured termini in the aggregation pathway of β2-microglobulin. Proteins Struct Funct Bioinf 85:2045–2057Google Scholar
  68. 68.
    Levinthal C (1968) Are there pathways for protein folding? J Chim Phys 65:44–45Google Scholar
  69. 69.
    Baldwin RL (1975) Intermediates in protein folding reactions and the mechanism of protein folding. Annu Rev Biochem 44:453–475PubMedGoogle Scholar
  70. 70.
    Wang Z, Mottonen J, Goldsmith EJ (1996) Kinetically controlled folding of the serpin plasminogen activator inhibitor 1. Biochemistry 35:16443–16448PubMedGoogle Scholar
  71. 71.
    Levinthal C (1969) How to fold graciously. In: Debrunnder JTP, Munck E (eds) Mossbauer spectroscopy in biological systems: proceedings of a meeting held at Allerton House, Monticello, Illinois, University of Illinois PressGoogle Scholar
  72. 72.
    Wetlaufer DB (1973) Nucleation, rapid folding, and globular intrachain regions in proteins. Proc Natl Acad Sci 70:697–701PubMedGoogle Scholar
  73. 73.
    Karplus M, Weaver DL (1979) Diffusion–collision model for protein folding. Biopolymers 18:1421–1437Google Scholar
  74. 74.
    Dill KA (1985) Theory for the folding and stability of globular proteins. Biochemistry 24:1501–1509PubMedGoogle Scholar
  75. 75.
    Jackson SE (1998) How do small single-domain proteins fold? Fold Des 3:R81–R91PubMedGoogle Scholar
  76. 76.
    Jackson SE, Fersht AR (1991) Folding of chymotrypsin inhibitor 2. 1. Evid Two-state Transit Biochem 30:10428–10435Google Scholar
  77. 77.
    Tsong TY, Baldwin RL, McPhie P, Elson EL (1972) A sequential model of nucleation-dependent protein folding: kinetic studies of ribonuclease A. J Mol Biol 63:453–469PubMedGoogle Scholar
  78. 78.
    Abkevich VI, Gutin AM, Shakhnovich EI (1994) Specific nucleus as the transition state for protein folding: evidence from the lattice model. Biochemistry 33:10026–10036PubMedGoogle Scholar
  79. 79.
    Itzhaki LS, Otzen DE, Fersht AR (1995) The structure of the transition state for folding of chymotrypsin inhibitor 2 analysed by protein engineering methods: evidence for a nucleation-condensation mechanism for protein folding. J Mol Biol 254:260–288PubMedGoogle Scholar
  80. 80.
    Weikl TR, Dill KA (2007) Transition-states in protein folding kinetics: the structural interpretation of φ values. J Mol Biol 365:1578–1586PubMedGoogle Scholar
  81. 81.
    Fersht AR (1995) Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications. Proc Natl Acad Sci 92:10869–10873PubMedGoogle Scholar
  82. 82.
    Faísca PFN (2009) The nucleation mechanism of protein folding: a survey of computer simulation studies. J Phys Condens Matter 21:373102PubMedGoogle Scholar
  83. 83.
    Bryngelson JD, Wolynes PG (1987) Spin glasses and the statistical mechanics of protein folding. Proc Natl Acad Sci 84:7524–7528PubMedGoogle Scholar
  84. 84.
    Leopold PE, Montal M, Onuchic JN (1992) Protein folding funnels: a kinetic approach to the sequence-structure relationship. Proc Natl Acad Sci 89:8721–8725PubMedGoogle Scholar
  85. 85.
    Onuchic JN, Luthey-Schulten Z, Wolynes PG (1997) Theory of protein folding: the energy landscape perspective. Ann Rev Phys Chem 48:545–600PubMedGoogle Scholar
  86. 86.
    Bryngelson JD, Onuchic JN, Socci ND, Wolynes PG (1995) Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins Struct Funct Bioinf 21:167–195Google Scholar
  87. 87.
    Onuchic JN, Wolynes PG (2004) Theory of protein folding. Curr Opin Struct Biol 14:70–75PubMedGoogle Scholar
  88. 88.
    Dill KA, Bromberg S, Yue K, Chan HS, Ftebig KM, Yee DP, Thomas PD (1995) Principles of protein folding—a perspective from simple exact models. Protein Sci 4:561–602PubMedPubMedCentralGoogle Scholar
  89. 89.
    Dill KA, Chan HS (1997) From Levinthal to pathways to funnels. Nat Struct Mol Biol 4:10–19Google Scholar
  90. 90.
    Chan HS, Dill KA (1998) Protein folding in the landscape perspective: chevron plots and non-arrhenius kinetics. Proteins Struct Funct Bioinf 30:2–33Google Scholar
  91. 91.
    Dill KA (1999) Polymer principles and protein folding. Protein Sci 8:1166–1180PubMedPubMedCentralGoogle Scholar
  92. 92.
    Plaxco KW, Simons KT, Baker D (1998) Contact order, transition state placement and the refolding rates of single domain proteins (Edited by Wright PE). J Mol Biol 277:985–994Google Scholar
  93. 93.
    Plaxco KW, Simons KT, Ruczinski I, Baker D (2000) Topology, stability, sequence, and length: defining the determinants of two-state protein folding kinetics. Biochemistry 39:11177–11183PubMedGoogle Scholar
  94. 94.
    Gromiha MM, Selvaraj S (2001) Comparison between long-range interactions and contact order in determining the folding rate of two-state proteins: application of long-range order to folding rate prediction (Edited by Wright PE). J Mol Biol 310:27–32Google Scholar
  95. 95.
    Micheletti C (2003) Prediction of folding rates and transition-state placement from native-state geometry. Proteins Struct Funct Bioinf 51:74–84Google Scholar
  96. 96.
    Chiti F, Taddei N, White PM, Bucciantini M, Magherini F, Stefani M, Dobson CM (1999) Mutational analysis of acylphosphatase suggests the importance of topology and contact order in protein folding. Nat Struct Mol Biol 6:1005–1009Google Scholar
  97. 97.
    Riddle DS, Grantcharova VP, Santiago JV, Alm E, Ruczinski I, Baker D (1999) Experiment and theory highlight role of native state topology in SH3 folding. Nat Struct Mol Biol 6:1016–1024Google Scholar
  98. 98.
    Lindorff-Larsen K, Vendruscolo M, Paci E, Dobson CM (2004) Transition states for protein folding have native topologies despite high structural variability. Nat Struct Mol Biol 11:443–449PubMedGoogle Scholar
  99. 99.
    Jewett AI, Pande VS, Plaxco KW (2003) Cooperativity, smooth energy landscapes and the origins of topology-dependent protein folding rates. J Mol Biol 326:247–253PubMedGoogle Scholar
  100. 100.
    Paci E, Lindorff-Larsen K, Dobson CM, Karplus M, Vendruscolo M (2005) Transition state contact orders correlate with protein folding rates. J Mol Biol 352:495–500PubMedGoogle Scholar
  101. 101.
    Faisca PFN, Ball RC (2002) Topological complexity, contact order, and protein folding rates. J Chem Phys 117:8587–8591Google Scholar
  102. 102.
    Kaya H, Chan HS (2003) Contact order dependent protein folding rates: kinetic consequences of a cooperative interplay between favorable nonlocal interactions and local conformational preferences. Proteins Struct Funct Bioinf 52:524–533Google Scholar
  103. 103.
    Makarov DE, Plaxco KW (2003) The topomer search model: a simple, quantitative theory of two-state protein folding kinetics. Protein Sci (A Publication of the Protein Society) 12:17–26Google Scholar
  104. 104.
    Faísca PFN, Travasso RDM, Parisi A, Rey A (2012) Why do protein folding rates correlate with metrics of native topology? PLoS ONE 7:e35599PubMedPubMedCentralGoogle Scholar
  105. 105.
    Ivankov DN, Garbuzynskiy SO, Alm E, Plaxco KW, Baker D, Finkelstein AV (2003) Contact order revisited: influence of protein size on the folding rate. Protein Sci (A Publication of the Protein Society) 12:2057–2062Google Scholar
  106. 106.
    Galzitskaya OV, Garbuzynskiy SO, Ivankov DN, Finkelstein AV (2003) Chain length is the main determinant of the folding rate for proteins with three-state folding kinetics. Proteins Struct Funct Bioinf 51:162–166Google Scholar
  107. 107.
    Naganathan AN, Muñoz V (2005) Scaling of folding times with protein size. J Am Chem Soc 127:480–481PubMedGoogle Scholar
  108. 108.
    De Sancho D, Doshi U, Muñoz V (2009) Protein folding rates and stability: how much is there beyond size? J Am Chem Soc 131:2074–2075PubMedGoogle Scholar
  109. 109.
    Sułkowska Joanna I, Noel Jeffrey K, Ramírez-Sarmiento César A, Rawdon Eric J, Millett Kenneth C, Onuchic José N (2013) Knotting pathways in proteins. Biochem Soc Trans 41:523–527PubMedGoogle Scholar
  110. 110.
    Faísca PFN (2015) Knotted proteins: a tangled tale of structural biology. Comput Struct Biotechnol Jurnal 13:459–468Google Scholar
  111. 111.
    Jackson SE, Suma A, Micheletti C (2017) How to fold intricately: using theory and experiments to unravel the properties of knotted proteins. Curr Opin Struct Biol 42:6–14PubMedGoogle Scholar
  112. 112.
    Mallam AL, Jackson SE (2007) A comparison of the folding of two knotted proteins: YbeA and YibK. J Mol Biol 366:650–665PubMedGoogle Scholar
  113. 113.
    Wallin S, Zeldovich KB, Shakhnovich EI (2007) The folding mechanics of a knotted protein. J Mol Biol 368:884–893PubMedPubMedCentralGoogle Scholar
  114. 114.
    Škrbić T, Micheletti C, Faccioli P (2012) The role of non-native interactions in the folding of knotted proteins. PLoS Comput Biol 8:e1002504PubMedPubMedCentralGoogle Scholar
  115. 115.
    Soler MA, Faísca PFN (2012) How difficult is it to fold a knotted protein? In silico insights from surface-tethered folding experiments. PLoS ONE 7:e52343PubMedPubMedCentralGoogle Scholar
  116. 116.
    Beccara S, Škrbić T, Covino R, Micheletti C, Faccioli P (2013) Folding pathways of a knotted protein with a realistic atomistic force field. PLOS Comput Biol 9: e1003002PubMedPubMedCentralGoogle Scholar
  117. 117.
    Sułkowska JI, Sułkowski P, Onuchic J (2009) Dodging the crisis of folding proteins with knots. Proc Natl Acad Sci 106:3119–3124PubMedGoogle Scholar
  118. 118.
    Noel JK, Sułkowska JI, Onuchic JN (2010) Slipknotting upon native-like loop formation in a trefoil knot protein. Proc Natl Acad Sci 107:15403–15408PubMedGoogle Scholar
  119. 119.
    Noel JK, Onuchic JN, Sulkowska JI (2013) Knotting a protein in explicit solvent. J Phys Chem Lett 4:3570–3573Google Scholar
  120. 120.
    Lim NCH, Jackson SE (2015) Mechanistic insights into the folding of knotted proteins in vitro and in vivo. J Mol Biol 427:248–258PubMedGoogle Scholar
  121. 121.
    Mallam AL, Jackson SE (2012) Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins. Nat Chem Biol 8:147–153Google Scholar
  122. 122.
    Bustamante A, Sotelo-Campos J, Guerra DG, Floor M, Wilson CAM, Bustamante C, Báez M (2017) The energy cost of polypeptide knot formation and its folding consequences. Nat Commun 8:1581PubMedPubMedCentralGoogle Scholar
  123. 123.
    Soler MA, Rey A, Faisca PFN (2016) Steric confinement and enhanced local flexibility assist knotting in simple models of protein folding. Phys Chem Chem Phys 18:26391–26403PubMedGoogle Scholar
  124. 124.
    Niewieczerzal S, Sulkowska JI (2017) Knotting and unknotting proteins in the chaperonin cage: effects of the excluded volume. PLoS ONE 12:e0176744PubMedPubMedCentralGoogle Scholar
  125. 125.
    Mirny L, Shakhnovich E (2001) Evolutionary conservation of the folding nucleus (Edited by Fersht AR). J Mol Biol 308:123–129Google Scholar
  126. 126.
    Sułkowska JI, Noel JK, Onuchic JN (2012) Energy landscape of knotted protein folding. Proc Natl Acad Sci 109:17783–17788PubMedGoogle Scholar
  127. 127.
    Yu I, Mori T, Ando T, Harada R, Jung J, Sugita Y, Feig M (2016) Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm. eLife 5: e19274.  https://doi.org/10.7554/eLife.19274
  128. 128.
    Bhushan S, Gartmann M, Halic M, Armache J-P, Jarasch A, Mielke T, Berninghausen O, Wilson DN, Beckmann R (2010) α-Helical nascent polypeptide chains visualized within distinct regions of the ribosomal exit tunnel. Nat Struct Mol Biol 17:313Google Scholar
  129. 129.
    Chaney JL, Clark PL (2015) Roles for synonymous codon usage in protein biogenesis. Annual Rev Biophys 44:143–166Google Scholar
  130. 130.
    Labbadia J, Morimoto RI (2015) The biology of proteostasis in aging and disease. Annu Rev Biochem 84:435–464PubMedPubMedCentralGoogle Scholar
  131. 131.
    Jahn TR, Parker MJ, Homans SW, Radford SE (2006) Amyloid formation under physiological conditions proceeds via a native-like folding intermediate. Nat Struct Mol Biol 13:195Google Scholar
  132. 132.
    Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475:324PubMedGoogle Scholar
  133. 133.
    Mogk A, Bukau B, Kampinga HH (2018) Cellular handling of protein aggregates by disaggregation machines. Mol Cell 69:214–226PubMedGoogle Scholar
  134. 134.
    Horowitz S, Koldewey P, Stull F, Bardwell JC (2018) Folding while bound to chaperones. Curr Opin Struct Biol 48:1–5PubMedGoogle Scholar
  135. 135.
    Hayer-Hartl M, Bracher A, Hartl FU (2016) The GroEL–GroES chaperonin machine: a nano-cage for protein folding. Trends Biochem Sci 41:62–76PubMedGoogle Scholar
  136. 136.
    Chiti F (2006) Relative importance of hydrophobicity, net charge, and secondary structure propensities in protein aggregation. In: Uversky VN, Fink AL (eds) Protein misfolding, aggregation, and conformational diseases: Part A: Protein aggregation and conformational diseases. Springer, Boston, pp 43–59Google Scholar
  137. 137.
    Ventura S (2005) Sequence determinants of protein aggregation: tools to increase protein solubility. Microb Cell Fact 4:11PubMedPubMedCentralGoogle Scholar
  138. 138.
    Rousseau F, Schymkowitz J, Serrano L (2006) Protein aggregation and amyloidosis: confusion of the kinds? Curr Opin Struct Biol 16:118–126PubMedGoogle Scholar
  139. 139.
    Gregersen N, Bross P, Vang S, Christensen JH (2006) Protein misfolding and human disease. Annu Rev Genomics Hum Genet 7:103–124PubMedGoogle Scholar
  140. 140.
    Stoppini M, Bellotti V (2015) Systemic amyloidosis: lessons from β2-microglobulin. J Biol Chem 290:9951–9958PubMedPubMedCentralGoogle Scholar
  141. 141.
    Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366PubMedGoogle Scholar
  142. 142.
    Tanskanen M (2013) “Amyloid”—historical aspects. In: Feng D (ed) Amyloidosis. InTech, Rijeka, pp Ch. 01Google Scholar
  143. 143.
    Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Med 10:S10PubMedGoogle Scholar
  144. 144.
    Shewmaker F, McGlinchey RP, Wickner RB (2011) Structural insights into functional and pathological amyloid. J Biol Chem 286:16533–16540PubMedPubMedCentralGoogle Scholar
  145. 145.
    Astbury WT, Dickinson S, Bailey K (1935) The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem J 29(2351–2360):2351PubMedPubMedCentralGoogle Scholar
  146. 146.
    Xiao Y, Ma B (2015) Abeta(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nat Struct Mol Biol 22:499–505Google Scholar
  147. 147.
    Nelson R, Sawaya MR, Balbirnie M, Madsen AØ, Riekel C, Grothe R, Eisenberg D (2005) Structure of the cross-β spine of amyloid-like fibrils. Nature 435:773–778PubMedPubMedCentralGoogle Scholar
  148. 148.
    Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJW, McFarlane HT, Madsen AO, Riekel C, Eisenberg D (2007) Atomic structures of amyloid cross-[bgr] spines reveal varied steric zippers. Nature 447:453–457PubMedGoogle Scholar
  149. 149.
    Gazit E (2002) A possible role for π-stacking in the self-assembly of amyloid fibrils. FASEB J 16:77–83PubMedGoogle Scholar
  150. 150.
    Gremer L, Scholzel D, Schenk C, Reinartz E, Labahn J (2017) Fibril structure of amyloid-beta (1–42) by cryo-electron microscopy. Science 358:116–119PubMedPubMedCentralGoogle Scholar
  151. 151.
    Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, Crowther RA, Ghetti B, Goedert M, Scheres SHW (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547:185–190PubMedPubMedCentralGoogle Scholar
  152. 152.
    Li B, Ge P, Murray KA, Sheth P, Zhang M, Nair G, Sawaya MR (2018) Cryo-EM of full-length alpha-synuclein reveals fibril polymorphs with a common structural kernel. Nat Commun 9:3609PubMedPubMedCentralGoogle Scholar
  153. 153.
    Iadanza MG, Silvers R (2018) The structure of a beta2-microglobulin fibril suggests a molecular basis for its amyloid polymorphism. 9:4517Google Scholar
  154. 154.
    Tycko R (2014) Physical and structural basis for polymorphism in amyloid fibrils. Protein Sci 23:1528–1539PubMedPubMedCentralGoogle Scholar
  155. 155.
    Thirumalai D, Reddy G, Straub JE (2012) Role of water in protein aggregation and amyloid polymorphism. Acc Chem Res 45:83–92PubMedGoogle Scholar
  156. 156.
    Arce FT, Jang H, Ramachandran S, Landon PB, Nussinov R, Lal R (2011) Polymorphism of amyloid β peptide in different environments: implications for membrane insertion and pore formation. Soft Matter 7:5267–5273PubMedPubMedCentralGoogle Scholar
  157. 157.
    Sarell CJ, Woods LA, Su Y, Debelouchina GT, Ashcroft AE, Griffin RG, Stockley PG, Radford SE (2013) Expanding the repertoire of amyloid polymorphs by co-polymerization of related protein precursors. J Biol ChemGoogle Scholar
  158. 158.
    Pham CLL, Kwan AH, Sunde M (2014) Functional amyloid: widespread in Nature, diverse in purpose. Essays Biochem 56:207–219PubMedGoogle Scholar
  159. 159.
    Otzen D (2010) Functional amyloid. Prion 4:256–264PubMedPubMedCentralGoogle Scholar
  160. 160.
    Fowler DM, Koulov AV, Balch WE, Kelly JW (2007) Functional amyloid—from bacteria to humans. Trends Biochem Sci 32:217–224PubMedGoogle Scholar
  161. 161.
    Evans ML, Chapman MR (2014) Curli biogenesis: order out of disorder. Biochimica et Biophysica Acta (BBA)—Mol Cell Res 1843:1551–1558Google Scholar
  162. 162.
    Iconomidou VA, Vriend G, Hamodrakas SJ (2000) Amyloids protect the silkmoth oocyte and embryo. FEBS Lett 479:141–145PubMedGoogle Scholar
  163. 163.
    Maji SK, Perrin MH, Sawaya MR, Jessberger S, Vadodaria K, Rissman RA, Singru PS, Nilsson KPR, Simon R, Schubert D, Eisenberg D, Rivier J, Sawchenko P, Vale W, Riek R (2009) Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325:328–332PubMedPubMedCentralGoogle Scholar
  164. 164.
    Fowler DM, Koulov AV, Alory-Jost C, Marks MS, Balch WE, Kelly JW (2005) Functional amyloid formation within mammalian tissue. PLoS Biol 4:e6PubMedCentralGoogle Scholar
  165. 165.
    Smith JF, Knowles TPJ, Dobson CM, MacPhee CE, Welland ME (2006) Characterization of the nanoscale properties of individual amyloid fibrils. Proc Natl Acad Sci 103:15806–15811PubMedGoogle Scholar
  166. 166.
    Greenwald J, Riek R (2010) Biology of amyloid: structure, function, and regulation. Structure 18:1244–1260PubMedGoogle Scholar
  167. 167.
    Knowles TPJ, Mezzenga R (2016) Amyloid fibrils as building blocks for natural and artificial functional materials. Adv Mater 28:6546–6561PubMedGoogle Scholar
  168. 168.
    Scheibel T, Parthasarathy R, Sawicki G, Lin X-M, Jaeger H, Lindquist SL (2003) Conducting nanowires built by controlled self-assembly of amyloid fibers and selective metal deposition. Proc Natl Acad Sci 100:4527–4532PubMedGoogle Scholar
  169. 169.
    Nilsson MR (2004) Techniques to study amyloid fibril formation in vitro. Methods 34:151–160PubMedGoogle Scholar
  170. 170.
    Alberti S, Halfmann R, Lindquist S (2010) Biochemical, cell biological, and genetic assays to analyze amyloid and prion aggregation in yeast (Chap. 30). In: Methods in enzymology. Academic Press, pp 709–734Google Scholar
  171. 171.
    Sleutel M, Van den Broeck I, Van Gerven N, Feuillie C, Jonckheere W, Valotteau C, Dufrene YF, Remaut H (2017) Nucleation and growth of a bacterial functional amyloid at single-fiber resolution. Nat Chem Biol 13:902–908PubMedPubMedCentralGoogle Scholar
  172. 172.
    Giurleo JT, He X, Talaga DS (2008) β-Lactoglobulin assembles into amyloid through sequential aggregated intermediates. J Mol Biol 381:1332–1348PubMedGoogle Scholar
  173. 173.
    Thirumalai D, Klimov DK, Dima RI (2003) Emerging ideas on the molecular basis of protein and peptide aggregation. Curr Opin Struct Biol 13:146–159PubMedGoogle Scholar
  174. 174.
    Kelly JW (1998) The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr Opin Struct Biol 8:101–106PubMedGoogle Scholar
  175. 175.
    Mahler H-C, Friess W, Grauschopf U, Kiese S (2008) Protein aggregation: pathways, induction factors and analysis. J Pharm Sci 98:2909–2934Google Scholar
  176. 176.
    Chiti F, Dobson CM (2009) Amyloid formation by globular proteins under native conditions. Nat Chem Biol 5:15–22PubMedGoogle Scholar
  177. 177.
    Jahn TR, Parker MJ, Homans SW, Radford SE (2006) Amyloid formation under physiological conditions proceeds via a native-like folding intermediate. Nat Struct Mol Biol 13:195–201PubMedGoogle Scholar
  178. 178.
    Estácio SG, Krobath H, Vila-Viçosa D, Machuqueiro M, Shakhnovich EI, Faísca PFN (2014) A simulated intermediate state for folding and aggregation provides insights into ΔN6 β2-microglobulin amyloidogenic behavior. PLoS Comput Biol 10:e1003606PubMedPubMedCentralGoogle Scholar
  179. 179.
    Neudecker P, Robustelli P, Cavalli A, Walsh P, Lundström P, Zarrine-Afsar A, Sharpe S, Vendruscolo M, Kay LE (2012) Structure of an intermediate state in protein folding and aggregation. Science 336:362–366PubMedGoogle Scholar
  180. 180.
    Honda Ryo P, Xu M, Yamaguchi K-I, Roder H, Kuwata K (2015) A native-like intermediate serves as a branching point between the folding and aggregation pathways of the mouse prion protein. Structure 23:1735–1742PubMedPubMedCentralGoogle Scholar
  181. 181.
    Jahn TR, Radford SE (2008) Folding versus aggregation: polypeptide conformations on competing pathways. Arch Biochem Biophys 469:100–117PubMedPubMedCentralGoogle Scholar
  182. 182.
    Cohen SIA, Vendruscolo M, Dobson CM, Knowles TPJ (2012) From macroscopic measurements to microscopic mechanisms of protein aggregation. J Mol Biol 421:160–171PubMedGoogle Scholar
  183. 183.
    Buell AK, Dobson CM, Knowles TPJ (2014) The physical chemistry of the amyloid phenomenon: thermodynamics and kinetics of filamentous protein aggregation. Essays Biochem 56:11–39PubMedGoogle Scholar
  184. 184.
    Meisl G, Michaels TCT, Linse S, Knowles TPJ (2018) Kinetic analysis of amyloid formation. Methods Mol Biol 1779:181–196Google Scholar
  185. 185.
    Herrup K (2015) The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 18:794PubMedGoogle Scholar
  186. 186.
    Stefani M (2012) Structural features and cytotoxicity of amyloid oligomers: implications in Alzheimer’s disease and other diseases with amyloid deposits. Prog Neurobiol 99:226–245PubMedGoogle Scholar
  187. 187.
    Bucciantini M, Rigacci S, Stefani M (2014) Amyloid aggregation: role of biological membranes and the aggregate-membrane system. J Phys Chem Lett 5:517–527PubMedGoogle Scholar
  188. 188.
    Leal SS, Botelho HM, Gomes CM (2012) Metal ions as modulators of protein conformation and misfolding in neurodegeneration. Coord Chem Rev 256:2253–2270Google Scholar
  189. 189.
    Morriss-Andrews A, Shea J-E (2015) Computational studies of protein aggregation: methods and applications. Annu Rev Phys Chem 66:643–666PubMedGoogle Scholar
  190. 190.
    Balchin D, Hayer-Hartl M, Hartl FU (2016) In vivo aspects of protein folding and quality control. Science 353PubMedGoogle Scholar
  191. 191.
    Michelitsch MD, Weissman JS (2000) A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. Proc Natl Acad Sci 97:11910–11915PubMedGoogle Scholar
  192. 192.
    Bemporad F, Calloni G, Campioni S, Plakoutsi G, Taddei N, Chiti F (2006) Sequence and structural determinants of amyloid fibril formation. Acc Chem Res 39:620–627PubMedGoogle Scholar
  193. 193.
    De Baets G, Schymkowitz J, Rousseau F (2014) Predicting aggregation-prone sequences in proteins. Essays Biochem 56:41–52PubMedGoogle Scholar
  194. 194.
    Beerten J, Schymkowitz J, Rousseau F (2012) Aggregation prone regions and gatekeeping residues in protein sequences. Curr Top Med Chem 12:2470–2478PubMedGoogle Scholar
  195. 195.
    Uversky VN (2010) Targeting intrinsically disordered proteins in neurodegenerative and protein dysfunction diseases: another illustration of the D(2) concept. Expert Rev Proteomics 7:543–564PubMedPubMedCentralGoogle Scholar
  196. 196.
    Fernandez-Escamilla A-M, Rousseau F, Schymkowitz J, Serrano L (2004) Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nat Biotechnol 22:1302PubMedGoogle Scholar
  197. 197.
    Tartaglia GG, Vendruscolo M (2008) The Zyggregator method for predicting protein aggregation propensities. Chem Soc Rev 37:1395–1401PubMedGoogle Scholar
  198. 198.
    Conchillo-Solé O, de Groot NS, Avilés FX, Vendrell J, Daura X, Ventura S (2007) AGGRESCAN: a server for the prediction and evaluation of “hot spots” of aggregation in polypeptides. BMC Bioinf 8:65Google Scholar
  199. 199.
    Zambrano R, Jamroz M, Szczasiuk A, Pujols J, Kmiecik S, Ventura S (2015) AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures. Nucleic Acids Res 43:W306–W313PubMedPubMedCentralGoogle Scholar
  200. 200.
    Fändrich M, Dobson CM (2002) The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J 21:5682–5690PubMedPubMedCentralGoogle Scholar
  201. 201.
    Bartlett AI, Radford SE (2009) An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms. Nat Struct Mol Biol 16:582–588PubMedGoogle Scholar
  202. 202.
    Cristovao JS, Henriques BJ, Gomes CM (2019) Biophysical and spectroscopic methods for monitoring protein misfolding and amyloid aggregation. Methods Mol Biol 1873:3–18Google Scholar
  203. 203.
    Lucas TG, Gomes CM, Henriques BJ (2019) Thermal shift and stability assays of disease-related misfolded proteins using differential scanning fluorimetry. Methods Mol Biol 1873:255–264Google Scholar
  204. 204.
    Kelly SM, Jess TJ, Price NC (2005) How to study proteins by circular dichroism. Biochem Biophys Acta 1751:119–139PubMedGoogle Scholar
  205. 205.
    Barth A (2007) Infrared spectroscopy of proteins. Biochem Biophys Acta 1767:1073–1101PubMedGoogle Scholar
  206. 206.
    Correia AR, Adinolfi S, Pastore A, Gomes CM (2006) Conformational stability of human frataxin and effect of Friedreich’s ataxia-related mutations on protein folding. Biochem J 398:605–611PubMedPubMedCentralGoogle Scholar
  207. 207.
    Gade Malmos K, Blancas-Mejia LM, Weber B, Buchner J, Ramirez-Alvarado M, Naiki H, Otzen D (2017) ThT 101: a primer on the use of thioflavin T to investigate amyloid formation. Amyloid 24:1–16PubMedGoogle Scholar
  208. 208.
    Miyazawa S, Jernigan RL (1985) Estimation of effective interresidue contact energies from protein crystal structures: quasi-chemical approximation. Macromolecules 18:534–552Google Scholar
  209. 209.
    Taketomi H, Ueda Y, Gō N (1975) Studies on protein folding, unfolding and fluctuations by computer simulation. Int J Pept Protein Res 7:445–459PubMedGoogle Scholar
  210. 210.
    Sebastian Kmiecik, Dominik Gront, Michal Kolinski, Lukasz Wieteska, Aleksandra Elzbieta Dawid, Andrzej Kolinski, (2016) Coarse-Grained Protein Models and Their Applications. Chemical Reviews 116(14):7898–7936PubMedGoogle Scholar
  211. 211.
    Tozzini V (2005) Coarse-grained models for proteins. Curr Opin Struct Biol 15:144–150PubMedGoogle Scholar
  212. 212.
    Kmiecik S, Gront D, Kolinski M, Wieteska L, Dawid AE, Kolinski A (2016) Coarse-grained protein models and their applications. Chem Rev 116:7898–7936PubMedGoogle Scholar
  213. 213.
    Enciso M, Rey A (2010) A refined hydrogen bond potential for flexible protein models. J Chem Phys 132:235102PubMedGoogle Scholar
  214. 214.
    Holzgräfe C, Wallin S (2014) Smooth functional transition along a mutational pathway with an abrupt protein fold switch. Biophys J 107:1217–1225PubMedPubMedCentralGoogle Scholar
  215. 215.
    Ponder JW, Case DA (2003) Force fields for protein simulations. Adv Protein Chem 66:27–85PubMedGoogle Scholar
  216. 216.
    Snow CD, Nguyen H, Pande VS, Gruebele M (2002) Absolute comparison of simulated and experimental protein-folding dynamics. Nature 420:102–106PubMedGoogle Scholar
  217. 217.
    Sandro Bottaro, Kresten Lindorff-Larsen, (2018) Biophysical experiments and biomolecular simulations: A perfect match?. Science 361(6400):355–360PubMedGoogle Scholar
  218. 218.
    Sugita Y, Okamoto Y (1999) Replica-exchange molecular dynamics method for protein folding. Chem Phys Lett 314:141–151Google Scholar
  219. 219.
    Bowman GR, Voelz VA, Pande VS (2011) Taming the complexity of protein folding. Curr Opin Struct Biol 21:4–11PubMedPubMedCentralGoogle Scholar
  220. 220.
    Lane TJ, Shukla D, Beauchamp KA, Pande VS (2013) To milliseconds and beyond: challenges in the simulation of protein folding. Curr Opin Struct Biol 23:58–65PubMedGoogle Scholar
  221. 221.
    Shaw DE, Maragakis P, Lindorff-Larsen K, Piana S, Dror RO, Eastwood MP, Bank JA, Jumper JM, Salmon JK, Shan Y, Wriggers W (2010) Atomic-level characterization of the structural dynamics of proteins. Science 330:341–346PubMedGoogle Scholar
  222. 222.
    Dror RO, Young C, Shaw DE (2011) Anton, a special-purpose molecular simulation machine. In: Padua D (ed) Encyclopedia of parallel computing. Springer, Boston, pp 60–71Google Scholar

Copyright information

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Chemistry and Biochemistry, Faculty of SciencesBiosystems & Integrative Sciences Institute, University of LisbonLisbonPortugal
  2. 2.Department of Physics, Faculty of SciencesBiosystems & Integrative Sciences Institute, University of LisbonLisbonPortugal

Personalised recommendations