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Molecular and thermodynamic mechanisms for protein adaptation

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Abstract

Using thermal adaptation of enzymes as an example, we have proposed a molecular and thermodynamic model for protein adaptation. Key concepts: (1) The working mechanism of enzymatic reactions is not altered in protein adaptation, but the activity of the adapted enzyme is expressed under altered conditions. (2) The alteration of protein conformational stability induced by gene mutation is the fundamental cause of protein adaptation. (3) The population change in active conformations of enzymes induced by protein conformational stability in different temperature ranges is the major cause of protein adaptation. (4) The features of enzyme adaptation must be analyzed or judged by two different aspects: local population change in active conformations near a critical level of an environmental factor; and the position of the whole active conformational curve in the gradient of an environmental factor. (5) Protein adaptation represents a specific mechanism for protein regulation. Several other aspects of protein adaptation are also discussed and reviewed, and specific examples are given of enzymes showing particular types of adaptation.

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References

  • Åqvist J, Sočan J, Purg M (2020) Hidden conformational states and strange temperature optima in enzyme catalysis. Biochemistry 59(40):3844–3855

    Article  PubMed  Google Scholar 

  • Arcus VL, Prentice EJ, Hobbs JK, Mulholland AJ, Van der Kamp MW, Pudney CR, Parker EJ, Schipper LA (2016) On the temperature dependence of enzyme-catalyzed rates. Biochemistry 55(12):1681–1688

    Article  PubMed  CAS  Google Scholar 

  • Arnold FH, Wintrode PL, Miyazaki K, Gershenson A (2001) How enzymes adapt: lessons from directed evolution. Trends Biochem Sci 26:100–106

    Article  PubMed  CAS  Google Scholar 

  • Becktel WJ, Schellman JA (1987) Protein stability curves. Biopolymers 26:1859–1877

    Article  PubMed  CAS  Google Scholar 

  • Beers JM, Jayasundara N (2015) Antarctic notothenioid fish: what are the future consequences of “losses” and “gains” acquired during long-term evolution at cold and stable temperatures? J Exp Biol 218:1834–1845

    Article  PubMed  Google Scholar 

  • Beney L, Gervais P (2001) Influence of the fluidity of the membrane on the response of microorganisms to environmental stresses. Appl Microbiol Biotechnol 57(1):34–42

    PubMed  CAS  Google Scholar 

  • Berger VJ, Kharazova AD (1997) Mechanisms of salinity adaptations in marine molluscs. Interactions and adaptation strategies of marine organisms. Springer, Dordrecht, pp 115–126

    Chapter  Google Scholar 

  • Bismuto E, Nucci R, Febbraio F, Tanfani F, Gentile F, Briante R, Scire A, Bertoli E, Amodeo P (2004) Effects induced by mono-and divalent cations on protein regions responsible for thermal adaptation in β-glycosidase from Sulfolobus solfataricus. Eur Biophys J 33(1):38–49

    Article  PubMed  CAS  Google Scholar 

  • Bloom JD, Meyer MM, Meinhold P, Otey CR, MacMillan D, Arnold FH (2005) Evolving strategies for enzyme engineering. Curr Opin Struc Biol 15:447–452

    Article  CAS  Google Scholar 

  • Boehr DD, Nussinov R, Wright PE (2009) The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol 5:789–796

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cedervall P, Aulabaugh A, Geoghegan KF, McLellan TJ, Pandit J (2015) Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4. Proc Natl Acad Sci USA 112(12):E1414–E1422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Collins T, Roulling F, Piette F, Marx JC, Feller G, Gerday C, D’Amico S (2008) Fundamentals of cold-adapted enzymes. Psychrophiles: from biodiversity to biotechnology. Springer, Berlin, pp 211–227

    Chapter  Google Scholar 

  • Daniel RM, Peterson ME, Danson MJ, Price NC, Kelly SM, Monk CR, Weinberg CS, Oudshoorn ML, Lee CK (2010) The molecular basis of the effect of temperature on enzyme activity. Biochem J 425:353–360

    Article  CAS  Google Scholar 

  • De Simone A, Aprile FA, Dhulesia A, Dobson CM, Vendruscolo M (2015) Structure of a low-population intermediate state in the release of an enzyme product. Elife 4:e02777

    Article  PubMed Central  Google Scholar 

  • Elias M, Wieczorek G, Rosenne S, Tawfik DS (2014) The universality of enzymatic rate-temperature dependency. Trends Biochem Sci 39:1–7

    Article  PubMed  CAS  Google Scholar 

  • Etchebest C, Benros C, Bornot A, Camproux AC, De Brevern AG (2007) A reduced amino acid alphabet for understanding and designing protein adaptation to mutation. Eur Biophys J 36(8):1059–1069

    Article  PubMed  CAS  Google Scholar 

  • Falsone SF, Leptihn S, Osterauer A, Haslbeck M, Buchner J (2004) Oncogenic mutations reduce the stability of SRC kinase. J Mol Biol 344:281–291

    Article  PubMed  Google Scholar 

  • Fariselli P, Olmea O, Valencia A, Casadio R (2001) Prediction of contact maps with neural networks and correlated mutations. Protein Eng 14:835–843

    Article  PubMed  CAS  Google Scholar 

  • Fersht AR (1977) Enzyme structure and mechanism. WH Freeman, New York

    Google Scholar 

  • Fersht AR, Serrano L (1993) Principles of protein stability derived from protein engineering experiments. Curr Opin Struct Biol 3(1):75–83

    Article  CAS  Google Scholar 

  • Fields PA, Somero GN (1998) Hot spots in cold adaptation: localized increases in conformational flexibility in lactate dehydrogenase A4 orthologs of Antarctic notothenioid fishes. Proc Natl Acad Sci USA 95:11476–11481

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fields PA, Dong Y, Meng X, Somero GN (2015) Adaptations of protein structure and function to temperature: there is more than one way to “skin a cat.” J Exp Biol 218:1801–1811

    Article  PubMed  Google Scholar 

  • Gerday C, Aittaleb M, Arpigny JL, Baise E, Chessa JP, Garsoux G, Petrescu I, Feller G (1997) Psychrophilic enzymes: a thermodynamic challenge. Biochim Biophys Acta (BBA) Protein Struct Mol Enzymol 1342(2):119–131

    Article  CAS  Google Scholar 

  • Gether U, Seifert R, Ballesteros JA, Sanders-Bush E, Weinstein H, Kobilka BK (1997) structural instability of a constitutively active G protein-coupled receptor agonist-independent activation due to conformational flexibility. J Biol Chem 272:2587–2590

    Article  PubMed  CAS  Google Scholar 

  • Ghadessy FJ, Ramsay N, Boudsocq F, Loakes D, Brown A, Iwai S, Vaisman A, Woodgate R, Holliger P (2004) Generic expansion of the substrate spectrum of a DNA polymerase by directed evolution. Nat Biotechnol 22:755–759

    Article  PubMed  CAS  Google Scholar 

  • Guerois R, Nielsen JE, Serrano L (2002) Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J Mol Biol 320:369–387

    Article  PubMed  CAS  Google Scholar 

  • Hajdú I, Bőthe C, Szilágyi A, Kardos J, Gál P, Závodszky P (2008) Adjustment of conformational flexibility of glyceraldehyde-3-phosphate dehydrogenase as a means of thermal adaptation and allosteric regulation. Eur Biophys J 37(7):1139–1144

    Article  PubMed  Google Scholar 

  • Hammes GG (2002) Multiple conformational changes in enzyme catalysis. Biochemistry 41:8221–8228

    Article  PubMed  CAS  Google Scholar 

  • Hardman MJ (1981) The rate-determining step in the liver alcohol dehydrogenase-catalysed reduction of acetaldehyde is an isomerization of the enzyme. Biochem J 195:773–774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harris H (1971) Polymorphism and protein evolution. The neutral mutation-random drift hypothesis. J Med Genet 8:444–452

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hernandez G, Jenney FE, Adams MWW, LeMaster DM (2000) Millisecond time scale conformational flexibility in a hyperthermophile protein at ambient temperature. Proc Natl Acad Sci USA 97:3166–3170

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hiller R, Zhou ZH, Adams MW, Englander SW (1997) Stability and dynamics in a hyperthermophilic protein with melting temperature close to 200 C. Proc Natl Acad Sci USA 94(21):11329–11332

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Honaker MT, Acchione M, Sumida JP, Atkins WM (2011) Ensemble perspective for catalytic promiscuity calorimetric analysis of the active site conformational landscape of a detoxification enzyme. J Biol Chem 286:42770–42821

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Isaksen GV, Åqvist J, Brandsdal BO (2014) Protein surface softness is the origin of enzyme cold-adaptation of trypsin. PLoS Comput Biol 10:e1003813

    Article  PubMed  PubMed Central  Google Scholar 

  • Jaenicke R (1991) Protein stability and molecular adaptation to extreme conditions. EJB reviews. Springer, Berlin, pp 291–304

    Google Scholar 

  • Jencks WP (1975) Binding energy, specificity, and enzymic catalysis: the circe effect. Adv Enzymol Relat Areas Mol Biol 43:219–410

    PubMed  CAS  Google Scholar 

  • Karshikoff A, Nilsson L, Ladenstein R (2015) Rigidity versus flexibility: the dilemma of understanding protein thermal stability. FEBS J 282:3899–3917

    Article  PubMed  CAS  Google Scholar 

  • Khersonsky O, Roodveldt C, Tawfik DS (2006) Enzyme promiscuity: evolutionary and mechanistic aspects. Curr Opin Chem Biol 10:498–508

    Article  PubMed  CAS  Google Scholar 

  • Kjelsberg MA, Cotecchia S, Ostrowski J, Caron MG, Lefkowitz RJ (1992) Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation. J Biol Chem 267:1430–1433

    Article  PubMed  CAS  Google Scholar 

  • Liang ZX, Tsigos I, Lee T, Bouriotis V, Resing KA, Ahn NG, Klinman JP (2004) Evidence for increased local flexibility in psychrophilic alcohol dehydrogenase relative to its thermophilic homologue. Biochemistry 43:14676–14683

    Article  PubMed  CAS  Google Scholar 

  • Low PS, Bada JL, Somero GN (1973) Temperature adaptation of enzymes: roles of the free energy, the enthalpy, and the entropy of activation. Proc Natl Acad Sci USA 70(2):430–432

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Madern D, Ebel C, Zaccai G (2000) Halophilic adaptation of enzymes. Extremophiles 4(2):91–98

    Article  PubMed  CAS  Google Scholar 

  • Maisnier-Patin S, Andersson DI (2004) Adaptation to the deleterious effects of antimicrobial drug resistance mutations by compensatory evolution. Res Microbiol 155:360–369

    Article  PubMed  CAS  Google Scholar 

  • Makhatadze GI, Privalov PL (1995) Energetics of protein structure. Adv Protein Chem 47:307–425

    Article  PubMed  CAS  Google Scholar 

  • Matthews BW (1993) Structural and genetic analysis of protein stability. Annu Rev Biochem 62:139–160

    Article  PubMed  CAS  Google Scholar 

  • Nagel ZD, Dong M, Bahnson BJ, Klinman JP (2011) Impaired protein conformational landscapes as revealed in anomalous Arrhenius prefactors. Proc Natl Acad Sci USA 108:10520–10525

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Olivares I, Sánchez-Merino V, Martínez MA, Domingo E, López-Galíndez C, Menéndez-Arias L (1999) Second-site reversion of a human immunodeficiency virus type 1 reverse transcriptase mutant that restores enzyme function and replication capacity. J Virol 73(8):6293–6298

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pace CN (1975) The stability of globular proteins. CRC Crit Rev Biochem 3:1–43

    Article  PubMed  CAS  Google Scholar 

  • Pace CN (1992) Contributions of the hydrophobic effect to globular protein stability. J Mol Biol 226:29–35

    Article  PubMed  CAS  Google Scholar 

  • Pace CN, Shirley BA, McNutt M, Gajiwala K (1996) Forces contributing to the conformational stability of proteins. FASEB J 10(1):75–83

    Article  PubMed  CAS  Google Scholar 

  • Page MJ, Cera ED (2006) Role of Na+ and K+ in enzyme function. Physiol Rev 86(4):1049–1092

    Article  PubMed  CAS  Google Scholar 

  • Pischedda A, Ramasamy KP, Mangiagalli M, Chiappori F, Milanesi L, Miceli C, Pucciarelli S, Lotti M (2018) Antarctic marine ciliates under stress: superoxide dismutases from the psychrophilic Euplotes focardii are cold-active yet heat tolerant enzymes. Sci Rep 8:1–13

    Article  CAS  Google Scholar 

  • Prevost M, Wodak SJ, Tidor B, Karplus M (1991) Contribution of the hydrophobic effect to protein stability: analysis based on simulations of the Ile-96-Ala mutation in barnase. Proc Natl Acad Sci USA 88:10880–10884

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Privalov PL (1990) Cold denaturation of protein. Crit Rev Biochem Mol Biol 25:281–306

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen SG, Jensen AD, Liapakis G, Ghanouni P, Javitch JA, Gether U (1999) Mutation of a highly conserved aspartic acid in the β2 adrenergic receptor: constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6. Mol Pharm 56:175–184

    Article  CAS  Google Scholar 

  • Saavedra HG, Wrabl JO, Anderson JA, Li J, Hilser VJ (2018) Dynamic allostery can drive cold adaptation in enzymes. Nature 558:324–328

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Scheer A, Fanelli F, Costa T, De Benedetti PG, Cotecchia S (1996) Constitutively active mutants of the alpha 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation. EMBO J 15:3566–3578

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shukla H, Shukla R, Sonkar A, Pandey T, Tripathi T (2017) Distant Phe345 mutation compromises the stability and activity of Mycobacterium tuberculosis isocitrate lyase by modulating its structural flexibility. Sci Rep 7:1–11

    Article  Google Scholar 

  • Somero GN (1995) Proteins and temperature. Annu Rev Physiol 57(1):43–68

    Article  PubMed  CAS  Google Scholar 

  • Stiller JB, Otten R, Häussinger D, Rieder PS, Theobald DL, Kern D (2022) Structure determination of high-energy states in a dynamic protein ensemble. Nature. https://doi.org/10.1038/s41586-022-04468-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Suzuki T, Yasugi M, Arisaka F, Yamagishi A, Oshima T (2001) Adaptation of a thermophilic enzyme, 3-isopropylmalate dehydrogenase, to low temperatures. Protein Eng 14:85–91

    Article  PubMed  CAS  Google Scholar 

  • Takagi Y, Taira K (1995) Temperature-dependent change in the rate-determining step in a reaction catalyzed by a hammerhead ribozyme. FEBS Lett 361:273–276

    Article  PubMed  CAS  Google Scholar 

  • Tattersall GJ, Sinclair BJ, Withers PC, Fields PA, Seebacher F, Cooper CE, Maloney SK (2012) Coping with thermal challenges: physiological adaptations to environmental temperatures. Compr Physiol 2(3):2151–2202

    Article  PubMed  Google Scholar 

  • Tokuriki N, Stricher F, Schymkowitz J, Serrano L, Tawfik DS (2007) The stability effects of protein mutations appear to be universally distributed. J Mol Biol 369:1318–1332

    Article  PubMed  CAS  Google Scholar 

  • Traut TW (1994) Dissociation of enzyme oligomers: a mechanism for allosteric regulation. Crit Rev Biochem Mol Biol 29:125–163

    Article  PubMed  CAS  Google Scholar 

  • Truhlar DG, Kohen A (2001) Convex Arrhenius plots and their interpretation. Proc Natl Acad Sci USA 98(3):848–851

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vieille C, Zeikus GJ (2001) Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability. Microbiol Mol Biol Rev 65:1–43

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vogt G, Woell S, Argos P (1997) Protein thermal stability, hydrogen bonds, and ion pairs. J Mol Biol 269:631–643

    Article  PubMed  CAS  Google Scholar 

  • Vyazovkin S (2000) Kinetic concepts of thermally stimulated reactions in solids: a view from a historical perspective. Int Rev Phys Chem 19(1):45–60

    Article  CAS  Google Scholar 

  • Warshel A, Sharma PK, Kato M, Parson WW (2006) Modeling electrostatic effects in proteins. Biochim Biophys Acta -Proteins and Proteomics 1764:1647–1676

    Article  CAS  Google Scholar 

  • Worth CL, Gong S, Blundell TL (2009) Structural and functional constraints in the evolution of protein families. Nat Rev Mol Cell Biol 10:709–720

    Article  PubMed  CAS  Google Scholar 

  • Xie Y, An J, Yang G, Wu G, Zhang Y, Cui L, Feng Y (2014) Enhanced enzyme kinetic stability by increasing rigidity within the active site. J Biol Chem 289:7994–8006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zavodszky P, Kardos J, Svingor PGA (1998) Adjustment of conformational flexibility is a key event in the thermal adaptation of proteins. Proc Natl Acad Sci USA 95:7406–7411

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhao Q (2009) Protein thermodynamic structure. IUBMB Life 61:600–606

    Article  PubMed  CAS  Google Scholar 

  • Zhao Q (2011) Dynamic model of enzymes action. Protein Pept Lett 18:92–99

    Article  PubMed  Google Scholar 

  • Zhao Q (2012) Partition function of the protein conformational state. J Comput Theor Nanos 9:745–751

    Article  CAS  Google Scholar 

  • Zhao Q (2015) A thermodynamic and theoretical view for enzyme regulation. Biochem Mosc 80:1–7

    Article  CAS  Google Scholar 

  • Zhao Q (2016) Classification of enzyme regulators within thermodynamic model of enzyme regulation. Mol Enz Drug Tar 2:14

    Article  Google Scholar 

  • Zhao Q (2017a) The origin of natural order: an axiomatic theory of biology. World Scientific Press, Singapore

    Book  Google Scholar 

  • Zhao Q (2017b) On the indirect relationship between protein dynamics and enzyme activity. Prog Biophys Mol Biol 125:52–60

    Article  PubMed  CAS  Google Scholar 

  • Zhao Q (2018) Physical characteristics of complex thermal system and working mechanism of enzymes. Sci Sin Vitae 48:650–661

    Article  Google Scholar 

  • Zhao Q (2022) Revised equation of enzymatic kinetics and thermodynamic mechanisms for directed evolution of enzymes. Int J Chem Kinet. https://doi.org/10.1002/kin.21558

    Article  CAS  Google Scholar 

  • Zhao L, Vogt PK (2008) Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci USA 105:2652–2657

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou H, Zhou Y (2002) Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction. Protein Sci 11:2714–2726

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

I would like to thank Professor Robert Gilbert (Wellcome Trust Centre for Human Genetics, University of Oxford, UK) for his help in the writing of this manuscript.

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  1. Medical Institute, CRRC, Beijing, People’s Republic of China

    Qinyi Zhao

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Zhao, Q. Molecular and thermodynamic mechanisms for protein adaptation. Eur Biophys J 51, 519–534 (2022). https://doi.org/10.1007/s00249-022-01618-9

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