Journal of Biomolecular NMR

, Volume 57, Issue 2, pp 155–166 | Cite as

Practical considerations over spectral quality in solid state NMR spectroscopy of soluble proteins

  • Marco Fragai
  • Claudio Luchinat
  • Giacomo Parigi
  • Enrico Ravera


Great theoretical and methodological advances are pushing the limits of resolution and sensitivity in solid state NMR (SSNMR). However, sample preparation remains a critical issue for the success of an experiment. The factors affecting spectral quality in SSNMR samples are discussed, examining cases encountered in the literature and presenting new experimental data. A discussion on resolution and sensitivity in sedimented solutes is framed in this context.


Ultracentrifuge Sedimentation Solid state NMR Sample preparation Frozen solution Cryoprotection Ubiquitin Superoxide dismutase 



Discussions with Lyndon Emsley, Moreno Lelli, Guido Pintacuda and Robert G. Griffin on resolution in SSNMR and with Vito Calderone on crystallization conditions are acknowledged. This work has been supported by Ente Cassa di Risparmio di Firenze, the European Commission (contract Bio-NMR no. 261863), and Instruct, part of the European Strategy Forum on Research Infrastructures (ESFRI) and supported by national member subscriptions. Specifically, we thank the EU ESFRI Instruct Core Centre CERM, Italy.

Supplementary material

10858_2013_9776_MOESM1_ESM.doc (72 kb)
Supplementary material 1 (DOC 72 kb)


  1. Akbey Ü, Franks T, Linden A, Lange S, Griffin RG, van Rossum B-J, Oschkinat H (2010a) Dynamic nuclear polarization of deuterated proteins. Angew Chem Int Ed 49:7803–7806Google Scholar
  2. Akbey Ü, Lange S, Franks WT, Linser R, Rehbein K, Diehl A, van Rossum BJ, Reif B, Oschkinat H (2010b) Optimum levels of exchangeable protons in perdeuterated proteins for proton detection in MAS solid-state NMR spectroscopy. J Biomol NMR 46:67–73Google Scholar
  3. Allen PJ, Creuzet F, de Groot HJM, Griffin RG (1991) Apparatus for low-temperature magic-angle spinning NMR. J Magn Reson 92:614–617ADSGoogle Scholar
  4. Andersson KM, Hovmoller S (2000) The protein content in crystals and packing coefficients in different space groups. Acta Crystallogr D Biol Crystallogr 56:789–790Google Scholar
  5. Asami S, Szekely K, Schanda P, Meier BH, Reif B (2012) Optimal degree of protonation for (1)H detection of aliphatic sites in randomly deuterated proteins as a function of the MAS frequency. J Biomol NMR 54:155–168Google Scholar
  6. Auger M, McDermott AE, Robinson V, Castelhano AL, Billedeau RJ, Pliura DH, Krantz A, Griffin RG (1993) Solid-state carbon-13 NMR study of a transglutaminase-inhibitor adduct. Biochemistry 32:3930–3934Google Scholar
  7. Balayssac S, Bertini I, Falber K, Fragai M, Jehle S, Lelli M, Luchinat C, Oschkinat H, Yeo KJ (2007) Solid-state NMR of matrix metalloproteinase 12: an approach complementary to solution NMR. ChemBioChem 8:486–489Google Scholar
  8. Baldwin AJ, Walsh P, Hansen DF, Hilton GR, Benesch JLP, Sharpe S, Kay LE (2012) Probing dynamic conformations of the high-molecular-weight αB-crystallin heat shock protein ensemble by NMR spectroscopy. J Am Chem Soc 134:15343–15350Google Scholar
  9. Banci L, Bencini A, Bertini I, Luchinat C, Piccioli M (1990) 1H NOE and ligand field studies of copper-cobalt superoxide dismutase with anions. Inorg Chem 29:4867–4873Google Scholar
  10. Banci L, Bertini I, Girotto S, Martinelli M, Vieru M, Whitelegge J, Durazo A, Valentine JS (2007) Metal-free SOD1 forms amyloid-like oligomers: a possible general mechanism for familial ALS. Proc Natl Acad Sci USA 104:11263–11267ADSGoogle Scholar
  11. Banci L, Bertini I, Boca M, Girotto S, Martinelli M, Valentine JS, Vieru M (2008) SOD1 and amyotrophic lateral sclerosis: mutations and oligomerization. PLoS One 3:e1677ADSGoogle Scholar
  12. Barbet-Massin E, Pell AJ, Knight MJ, Webber AL, Felli IC, Pierattelli R, Emsley L, Lesage A, Pintacuda G (2013) 13C-detected through-bond correlation experiments for protein resonance assignment by ultra-fast MAS NMR. ChemPhysChem. doi:10.1002/cphc.201201097
  13. Barnes AB, De Paëpe G, Van der Wel PCA, Hu K-N, Joo C-G, Bajaj VS, Mak-Jurkauskas ML, Sirigiri JR, Herzfeld J, Temkin RJ, Griffin RG (2008) High-field dynamic nuclear polarization for solid and solution biological NMR. Appl Magn Reson 34:237–263Google Scholar
  14. Barnes AB, Mak-Jurkauskas ML, Matsuki Y, Bajaj VS, Van der Wel PCA, DeRocher R, Bryant J, Sirigiri JR, Temkin RJ, Lugtenburg J, Herzfeld J, Griffin RG (2009) Cryogenic sample exchange NMR probe for magic angle spinning dynamic nuclear polarization. J Magn Reson 198:261–270ADSGoogle Scholar
  15. Bayro MJ, Debelouchina GT, Eddy MT, Birkett NR, MacPhee CE, Rosay MM, Maas W, Dobson CM, Griffin RG (2011) Intermolecular structure determination of amyloid fibrils with magic-angle spinning and dynamic nuclear polarization NMR. J Am Chem Soc 133:13967–13974Google Scholar
  16. Benvenuti M, Mangani S (2007) Crystallisation of soluble proteins in vapour diffusion for X-ray crystallography. Nat Protoc 2:1633–1651Google Scholar
  17. Bertini I, Luchinat C, Parigi G (2001) Solution NMR of paramagnetic molecules. Elsevier, AmsterdamGoogle Scholar
  18. Bertini I, Bhaumik A, De Paepe G, Griffin RG, Lelli M, Lewandowski JR, Luchinat C (2010) High-resolution solid-state NMR structure of a 17.6 kDa protein. J Am Chem Soc 132:1032–1040Google Scholar
  19. Bertini I, Gonnelli L, Luchinat C, Mao J, Nesi A (2011a) A new structural model Aß40 fibrils. J Am Chem Soc 133:16013–16022Google Scholar
  20. Bertini I, Luchinat C, Parigi G, Ravera E, Reif B, Turano P (2011b) Solid-state NMR of proteins sedimented by ultracentrifugation. Proc Natl Acad Sci USA 108:10396–10399ADSGoogle Scholar
  21. Bertini I, Engelke F, Gonnelli L, Knott B, Luchinat C, Osen D, Ravera E (2012a) On the use of ultracentrifugal devices for sedimented solute NMR. J Biomol NMR 54:123–127Google Scholar
  22. Bertini I, Engelke F, Luchinat C, Parigi G, Ravera E, Rosa C, Turano P (2012b) NMR properties of sedimented solutes. Phys Chem Chem Phys 14:439–447Google Scholar
  23. Bertini I, Gallo G, Korsak M, Luchinat C, Mao J, Ravera E (2013a) Formation kinetics and structural features of beta-amyloid aggregates by sedimented solute NMR. ChemBioChem. doi:10.1002/cbic.201300141
  24. Bertini I, Luchinat C, Parigi G, Ravera E (2013b) SedNMR: on the edge between solution and solid state NMR. Acc Chem Res. doi:10.1021/ar300342f
  25. Böckmann A, Gardiennet C, Verel R, Hunkeler A, Loquet A, Pintacuda G, Emsley L, Meier BH, Lesage A (2009) Characterization of different water pools in solid-state NMR protein samples. J Biomol NMR 45:319–327Google Scholar
  26. Castellani F, van Rossum B, Diehl A, Schubert M, Rehbein K, Oschkinat H (2002) Structure of a protein determined by solid-state magic-angle-spinning NMR spectroscopy. Nature 420:98–102ADSGoogle Scholar
  27. Chatelier RC, Minton AP (1987) Sedimentation equilibrium in macromolecular solutions of arbitrary concentration. I. Self-associating proteins. Biopolymers 26:507–524Google Scholar
  28. Cole HBR, Torchia DA (1991) An NMR study of the backbone dynamics of staphylococcal nuclease in the crystalline state. Chem Phys 158:271–281ADSGoogle Scholar
  29. Concistre M, Johannessen OG, Carignani E, Geppi M, Levitt M (2013) Magic-angle spinning NMR of cold samples. Acc Chem Res. doi:10.1021/ar300323c
  30. Corzilius B, Smith AA, Barnes AB, Luchinat C, Bertini I, Griffin RG (2011) High-filed dynamic nuclear polarization with high spin transition metal ions. J Am Chem Soc 133:5648–5651Google Scholar
  31. Corzilius B, Smith AA, Griffin RG (2012) Solid effect in magic angle spinning dynamic nuclear polarization. J Chem Phys 173:054201ADSGoogle Scholar
  32. Cross TA, Opella SJ (1983) Protein structure by solid-state NMR. J Am Chem Soc 105:306–308Google Scholar
  33. de la Torre JG, Huertas ML, Carrasco B (2000) Calculation of hydrodynamic properties of globular proteins from their atomic-level structure. Biophys J 78:719–730Google Scholar
  34. Debelouchina GT, Platt GW, Bayro MJ, Radford SE, Griffin RG (2010) Magic angle spinning NMR analysis of beta(2)-microglobulin amyloid fibrils in two distinct morphologies. J Am Chem Soc 132:10414–10423Google Scholar
  35. Denisov VP, Venu K, Peters J, Horlein HD, Halle B (1997) Orientational disorder and entropy of water in protein cavities. J Phys Chem B 101:9380–9389Google Scholar
  36. Diakova G, Goddard YA, Korb J-P, Bryant RG (2010) Water and backbone dynamics in a hydrated protein. Biophys J 98:138–146Google Scholar
  37. Doucette PA, Whitson LJ, Cao X, Schirf V, Demeler B, Valentine JS, Hansen JC, Hart PJ (2004) Dissociation of human copper-zinc superoxide dismutase dimers using chaotrope and reductant. Insights into the molecular basis for dimer stability. J Biol Chem 279:54558–54566Google Scholar
  38. Franks WT, van Rossum B-J, Bardiaux B, Ravera E, Parigi G, Luchinat C, Oschkinat H (2012) In: Bertini I, McGreevy KS, Parigi G (eds) NMR of biomolecules: towards mechanistic systems biology. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 376–392Google Scholar
  39. Gardiennet C, Schütz AK, Hunkeler A, Kunert B, Terradot L, Böckmann A, Meier BH (2012) A sedimented sample of a 59 kDa dodecameric helicase yields high-resolution solid-state NMR spectra. Angew Chem Int Ed 51:7855–7858Google Scholar
  40. Gelis I, Vitzthum V, Dhimole N, Caporini MA, Schedlbauer A, Carnevale D, Connell SR, Fucini P, Bodenhausen G (2013) Solid-state NMR enhanced by dynamic nuclear polarization as a novel tool for ribosome structural biology. J Biomol NMR 56:85–93Google Scholar
  41. Goddard YA, Korb J-P, Bryant RG (2009) Water molecule contributions to proton spin-lattice relaxation in rotationally immobilized proteins. J Magn Reson 199:68–74ADSGoogle Scholar
  42. Ha Y, Shi D, Small GW, Theil EC, Allewell NM (1999) Crystal structure of bullfrog M ferritin at 2.8 Å resolution: analysis of subunit interactions and the binuclear metal center. J Biol Inorg Chem 4:243–256Google Scholar
  43. Hall DA, Maus DC, Gerfen GJ, Inati SJ, Becerra LR, Dahlquist FW, Griffin RG (1997) Polarizarion-enhanced NMR spectroscopy of biomolecules in frozen solution. Science 276:930–932Google Scholar
  44. Harbison GS, Smith SO, Pardoen JA, Courtin JML, Lugtenburg J, Herzfeld J, Mathies RA, Griffin RG (1985) Solid-state carbon-13 NMR detection of a perturbed 6-s-trans chromophore in bacteriorhodopsin. Biochemistry 24:6955–6962Google Scholar
  45. Havlin RH, Tycko R (2005) Probing site-specific conformational distributions in protein folding with solid-state NMR. Proc Natl Acad Sci USA 102:3284–3289ADSGoogle Scholar
  46. Hefke F, Bagaria A, Reckel S, Ullrich SJ, Dötsch V, Glaubitz C, Güntert P (2011) Optimization of amino acid type-specific 13C and 15N labeling for the backbone assignment of membrane proteins by solution- and solid-state NMR with the UPLABEL algorithm. J Biomol NMR 49:75–84Google Scholar
  47. Hills BP (1992) The proton exchange cross-relaxation model of water relaxation in biopolymer systems. Mol Phys 76:489–508ADSGoogle Scholar
  48. Hu KN, Yu HH, Swager TM, Griffin RG (2004) Dynamic nuclear polarization with biradicals. J Am Chem Soc 126:10844–10845Google Scholar
  49. Hu K-N, Bajaj VS, Rosay M, Griffin RG (2007) High-frequency dynamic nuclear polarization using mixtures of TEMPO and trityl radicals. J Chem Phys 126:44512-1–44512-7Google Scholar
  50. Hu K-N, Yau W-M, Tycko R (2010) Detection of a transient intermediate in a rapid protein folding process by solid-state nuclear magnetic resonance. J Am Chem Soc 132:24–25Google Scholar
  51. Huang TH, Bachovchin WW, Griffin RG, Dobson CM (1984) High-resolution nitrogen-15 nuclear magnetic resonance studies of α-lytic protease in solid state. Direct comparison of enzyme structure in solution and solid states. Biochemistry 23:5933–5937Google Scholar
  52. Huang K-Y, Amodeo GA, Tong L, McDermott AE (2011) The structure of human ubiquitin in 2-methyl-2,4-pentanediol: a new conformational switch. Protein Sci 20:630–639Google Scholar
  53. Igumenova TI, McDermott AE, Zilm KW, Martin RW, Paulson EK, Wand AJ (2004a) Assignments of carbon NMR resonances for microcrystalline ubiquitin. J Am Chem Soc 126:6720–6727Google Scholar
  54. Igumenova TI, Wand AJ, McDermott AE (2004b) Assignment of the backbone resonances for microcrystalline ubiquitin. J Am Chem Soc 126:5323–5331Google Scholar
  55. Ivins FJ, Montgomery MG, Smith SJM, Morris-Davies AC, Taylor IA, Rittinger K (2009) NEMO oligomerization and its ubiquitin-binding properties. Biochem J 421:243–251Google Scholar
  56. Jakeman DL, Mitchell DJ, Shuttleworth WA, Evans JNS (1998) Effects of sample preparation conditions on biomolecular solid-state NMR lineshapes. J Biomol NMR 12:417–421Google Scholar
  57. Kantardjieff KA, Rupp B (2003) Matthews coefficient probabilities: improved estimates for unit cell contents of proteins, DNA, and protein-nucleic acid complex crystals. Protein Sci 12:1865–1871Google Scholar
  58. Keniry MA, Rothgeb TM, Smith RL, Gutowsky HS, Oldfield E (1983) NMR studies of amino acids and proteins. Side-chain mobility of methionine in the crystalline amino acid and in crystalline sperm whale (Physeter catodon) myoglobin. Biochemistry 22:1917–1926Google Scholar
  59. Kiihne S, Bryant RG (2000) Protein-bound water molecule counting by resolution of 1H spin-lattice relaxation mechanisms. Biophys J 78:2163–2169Google Scholar
  60. Knight MJ, Webber AL, Pell AJ, Guerry P, Barbet-Massin E, Bertini I, Felli IC, Gonnelli L, Pierattelli R, Emsley L, Lesage A, Hermann T, Pintacuda G (2011) Fast resonance assignment and fold determination of human superoxide dismutase by high-resolution proton-detected solid state MAS NMR spectroscopy. Angew Chem Int Ed 50:11697–11701Google Scholar
  61. Knight MJ, Felli IC, Pierattelli R, Bertini I, Emsley L, Hermann T, Pintacuda G (2012a) Rapid measurement of pseudocontact shifts in metalloproteins by proton-detected solid-state NMR spectroscopy. J Am Chem Soc 134:14730–14733Google Scholar
  62. Knight MJ, Pell AJ, Bertini I, Felli IC, Gonnelli L, Pierattelli R, Hermann T, Emsley L, Pintacuda G (2012b) Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR. Proc Natl Acad Sci USA 109:11095–11100ADSGoogle Scholar
  63. Knight MJ, Felli IC, Pierattelli R, Emsley L, Pintacuda G (2013) Magic angle spinning NMR of paramagnetic proteins. Acc Chem Res. doi:10.1021/ar300349y
  64. Laage S, Marchetti A, Sein J, Pierattelli R, Sass HJ, Grzesiek S, Lesage A, Pintacuda G, Emsley L (2008) Band-selective 1H–13C cross-polarization in fast MAS solid-state NMR spectroscopy. J Am Chem Soc 130:17216–17217Google Scholar
  65. Laage S, Lesage A, Emsley L, Bertini I, Felli IC, Pierattelli R, Pintacuda G (2009a) Transverse-dephasing optimized homonuclear J-decoupling in solid-state NMR spectroscopy of uniformly 13C-labeled proteins. J Am Chem Soc 131:10816–10817Google Scholar
  66. Laage S, Sachleben J, Steuernagel S, Pierattelli R, Pintacuda G, Emsley L (2009b) Fast acquisition of multi-dimensional spectra in solid-state NMR enabled by ultra-fast MAS. J Magn Reson 196:133–141ADSGoogle Scholar
  67. Lee AL, Wand AJ (1999) Assessing potential bias in the determination of rotational correlation times of proteins by NMR relaxation. J Biomol NMR 13:101–112Google Scholar
  68. Lewandowski JR, Sein J, Sass HJ, Grzesiek S, Blackledge M, Emsley L (2010) Measurement of site-specific 13C spin-lattice relaxation in a crystalline protein. J Am Chem Soc 132:8252–8254Google Scholar
  69. Lewandowski JR, Dumez JN, Akbey Ü, Franks WT, Emsley L, Oschkinat H (2011a) Enhanced resolution and coherence lifetimes in the solid-state NMR spectroscopy of perdeuterated proteins under ultrafast magic-angle spinning. J Phys Chem Lett 2:2205–2211Google Scholar
  70. Lewandowski JR, Sass HJ, Grzesiek S, Blackledge M, Emsley L (2011b) Site-specific measurement of slow motions in proteins. J Am Chem Soc 133:16762–16765Google Scholar
  71. Lewandowski JR, Van der Wel PCA, Rigney M, Grigorieff N, Griffin RG (2011c) Structural complexity of a composite amyloid fibril. J Am Chem Soc 133:14686–14698Google Scholar
  72. Libralesso E, Nerinovski K, Parigi G, Turano P (2005) 1H nuclear magnetic relaxation dispersion of Cu, Zn superoxide dismutase in the native and guanidinium-induced unfolded forms. Biochem Biophys Res Commun 328:633–639Google Scholar
  73. Linden AH, Franks WT, Akbey Ü, Lange S, van Rossum B-J, Oschkinat H (2011) Cryogenic temperature effects and resolution upon slow cooling of protein preparations in solid state NMR. J Biomol NMR 51:283–292Google Scholar
  74. Liu Z, Zhang W-P, Xing Q, Ren X, Liu M, Tang C (2012) Noncovalent dimerization of ubiquitin. Angew Chem Int Ed 51:469–472Google Scholar
  75. Loquet A, Giller K, Becker S, Lange A (2010) Supramolecular interactions probed by (13)C-(13)C solid-state NMR spectroscopy. J Am Chem Soc 132:15164–15166Google Scholar
  76. Loquet A, Sgourakis NG, Gupta R, Giller K, Riedel D, Goosmann C, Griesinger C, Kolbe M, Baker D, Becker S, Lange A (2012) Atomic model of the type III secretion system needle. Nature 486:276–279ADSGoogle Scholar
  77. Loquet A, Habenstein B, Lange A (2013) Structural investigations of molecular machines by solid-state NMR. Acc Chem Res. doi:10.1021/ar300320p
  78. Luchinat C, Parigi G, Ravera E, Rinaldelli M (2012) Solid state NMR crystallography through paramagnetic restraints. J Am Chem Soc 134:5006–5009Google Scholar
  79. Luchinat C, Parigi G, Ravera E (2013) Water and protein dynamics in sedimented systems: a relaxometric investigation. Chem Phys Chem. doi:10.1002/cphc.201300167
  80. Lundh S (1980) Concentrated protein solutions in the analytical ultracentrifuge. J Polym Sci Polym Phys Ed 18:1963–1978Google Scholar
  81. Lundh S (1985) Ultacentrifugation of concentrated biopolymer solutions and effect of ascorbate. Arch Biochem Biophys 241:265–274Google Scholar
  82. Lv G, Kumar A, Giller K, Orcellet ML, Riedel D, Fernandez CO, Becker S, Lange A (2012) Structural comparison of mouse and human α-synuclein amyloid fibrils by solid-state NMR. J Mol Biol 420:99–111Google Scholar
  83. Mainz A, Jehle S, van Rossum BJ, Oschkinat H, Reif B (2009) Large protein complexes with extreme rotational correlation times investigated in solution by magic-angle-spinning NMR spectroscopy. J Am Chem Soc 131:15968–15969Google Scholar
  84. Mainz A, Bardiaux B, Kuppler F, Multhaup G, Felli IC, Pierattelli R, Reif B (2012) Structural and mechanistic implications of metal-binding in the small heat-shock protein αB-crystallin. J Biol Chem 287:1128–1138Google Scholar
  85. Margiolaki I, Wright JP, Wilmanns M, Fitch AN, Pinotsis N (2007) Second SH3 domain of ponsin solved from powder diffraction. J Am Chem Soc 129:11865–11871Google Scholar
  86. Martin RW, Zilm KW (2003) Preparation of protein nanocrystals and their characterization by solid state NMR. J Magn Reson 165:162–174ADSGoogle Scholar
  87. Matsuki Y, Maly T, Ouari O, Karoui H, Le Moigne F, Rizzato E, Lyubenova S, Herzfeld J, Prisner TF, Tordo P, Griffin RG (2009) Dynamic nuclear polarization with a rigid biradical. Angew Chem Int Ed 121:5096–5100Google Scholar
  88. McDermott A (2009) Structure and dynamics of membrane proteins by magic angle spinning solid-state NMR. Annu Rev Biophys 38:385–403MathSciNetGoogle Scholar
  89. McDermott AE, Polenova T, Böckmann A, Zilm KW, Paulsen EK, Martin RW, Montelione GT (2000) Partial NMR assignments for uniformly (13C, 15N)-enriched BPTI in the solid state. J Biomol NMR 16:209–219Google Scholar
  90. Minton AP (2007) The effective hard particle model provides a simple, robust, and broadly applicable description of nonideal behavior in concentrated solutions of bovine serum albumin and other nonassociating proteins. J Pharm Sci 96:3466–3469Google Scholar
  91. Murray DT, Das N, Cross TA (2013) Solid state NMR strategy for characterizing native membrane protein structures. Acc Chem Res. doi:10.1021/ar3003442
  92. Ni QZ, Daviso E, Can TV, Markhasin E, Jawla SK, Swager TM, Temkin RJ, Herzfeld J, Griffin RG (2013) High frequency dynamic nuclear polarization. Acc Chem Res. doi:10.1021/ar300348n
  93. Paravastu AK, Leapman RD, Yau WM, Tycko R (2008) Molecular structural basis for polymorphism in Alzheimer’s beta-amyloid fibrils. Proc Natl Acad Sci USA 105:18349–18354ADSGoogle Scholar
  94. Pauli J, van Rossum B, Forster H, de Groot HJ, Oschkinat H (2000) Sample optimization and identification of signal patterns of amino acid side chains in 2D RFDR spectra of the alpha-spectrin SH3 domain. J Magn Reson 143:411–416ADSGoogle Scholar
  95. Petkova AT, Ishii Y, Balbach JJ, Antzutkin ON, Leapman RD, Delaglio F, Tycko R (2002) A structural model for Alzheimer’s beta-amyloid fibrils based on experimental constraints from solid state NMR. Proc Natl Acad Sci USA 99:16742–16747ADSGoogle Scholar
  96. Pines A, Gibby MG, Waugh JS (1972) Proton-enhanced nuclear induction spectroscopy. A method for high resolution NMR of dilute spins in solids. J Chem Phys 56:1776–1777ADSGoogle Scholar
  97. Qiang W, Yau W-M, Luo Y, Mattson MP, Tycko R (2012) Antiparallel β-sheet architecture in Iowa-mutant β-amyloid fibrils. Proc Natl Acad Sci USA 109:4443–4448ADSGoogle Scholar
  98. Ravera E, Corzilius B, Michaelis VK, Rosa C, Griffin RG, Luchinat C, Bertini I (2013a) Dynamic nuclear polarization of sedimented solutes. J Am Chem Soc 135:1641–1644Google Scholar
  99. Ravera E, Parigi G, Mainz A, Religa TL, Reif B, Luchinat C (2013b) Experimental determination of microsecond reorientation correlation times in protein solutions. J Phys Chem B 117:3548–3553Google Scholar
  100. Rivas G, Minton AP (2011) Beyond the second virial coefficient: sedimentation equilibrium in highly non-ideal solutions. Methods 54:167–174Google Scholar
  101. Rothgeb TM, Oldfield E (1981) Nuclear magnetic resonance of heme protein crystals. General aspects. J Biol Chem 256:1432–1446Google Scholar
  102. Salager E, Stein RS, Steuernagel S, Lesage A, Elena B, Emsley L (2009) Enhanced sensitivity in high-resolution 1H solid-state NMR spectroscopy with DUMBO dipolar decoupling under ultra-fastMAS. Chem Phys Lett 469:336–341ADSGoogle Scholar
  103. Seidel K, Etzkorn M, Heise H, Becker S, Baldus M (2005) High-resolution solid-state NMR studies on uniformly [13C,15N]-labeled ubiquitin. ChemBioChem 6:1638–1647Google Scholar
  104. Sengupta I, Nadaud PS, Jaroniec CP (2013) Protein structure determination with paramagnetic solid-state NMR spectroscopy. Acc Chem Res. doi:10.1021/ar300360q
  105. Sheng Y, Chattopadhyay M, Whitelegge JP, Valentine JS (2012) SOD1 aggregation and ALS: role of metallation states and disulfide status. Curr Top Med Chem 12:2560–2572Google Scholar
  106. Siemer AB, McDermott AE (2008) Solid-state NMR on a type III antifreeze protein in the presence of ice. J Am Chem Soc 130:17394–17399Google Scholar
  107. Siemer AB, Huang K-Y, McDermott AE (2012) Protein linewidth and solvent dynamics in froze solution NMR. PLoS One 7:e47242ADSGoogle Scholar
  108. Smith SO, Farr-Jones S, Griffin RG, Bachovchin WW (1989) Crystal versus solution structures of enzymes: NMR spectroscopy of a crystalline serine protease. Science 244:961–964ADSGoogle Scholar
  109. Thurber KR, Tycko R (2008) Biomolecular solid state NMR with magic-angle spinning at 25 K. J Magn Reson 195:179–186ADSGoogle Scholar
  110. Thurber KR, Tycko R (2009) Measurement of sample temperatures under magic-angle spinning from the chemical shift and spin-lattice relaxation rate of 79Br in KBr powder. J Magn Reson 196:84–87ADSGoogle Scholar
  111. Turano P, Lalli D, Felli IC, Theil EC, Bertini I (2010) NMR reveals a pathway for iron mineral precursors to the central cavity of ferritin. Proc Natl Acad Sci USA 107:545–550ADSGoogle Scholar
  112. Tycko R (2011) Solid-state NMR studies of amyloid fibril structure. Annu Rev Phys Chem 62:10–20Google Scholar
  113. Tycko R (2013) NMR at Low and Ultralow Temperatures. Acc Chem Res. doi:10.1021/ar300358z
  114. Van der Wel PC, Hu KN, Lewandowski J, Griffin RG (2006) Dynamic nuclear polarization of amyloidogenic peptide nanocrystals: GNNQQNY, a core segment of the yeast prion protein Sup35p. J Am Chem Soc 128:10840–10846Google Scholar
  115. Van der Wel PC, Lewandowski JR, Griffin RG (2007) Solid-state NMR study of amyloid nanocrystals and fibrils formed by the peptide GNNQQNY from yeast prion protein Sup35p. J Am Chem Soc 129:5117–5130Google Scholar
  116. Venturi L, Woodward N, Hibberd D, Marighedo N, Gravelle A, Ferrante G, Hills BP (2008) Multidimensional cross-correlation relaxometry of aqueous protein systems. Appl Magn Reson 33:213–234Google Scholar
  117. Venu K, Denisov VP, Halle B (1997) Water 1H magnetic relaxation dispersion in protein solutions. A quantitative assessment of internal hydration, proton exchange, and cross-relaxation. J Am Chem Soc 119:3122–3134Google Scholar
  118. Wasmer C, Lange A, Van Melckebeke H, Siemer AB, Riek R, Meier BH (2008) Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core. Science 319:1523–1526ADSGoogle Scholar
  119. Webber AL, Pell AJ, Barbet-Massin E, Knight MJ, Bertini I, Felli IC, Pierattelli R, Emsley L, Lesage A, Pintacuda G (2012) Combination of DQ and ZQ coherences for sensitive through-bond NMR correlation experiments in biosolids under ultra-fast MAS. ChemPhysChem 13:2405–2411Google Scholar
  120. Weis V, Griffin RG (2006) Electron-nuclear cross polarization. Solid State Nucl Magn Reson 29:66–78Google Scholar
  121. Yan S, Suiter CL, Hou G, Zhang H, Polenova T (2013) Probing structure and dynamics of protein assemblies by magic angle spinning NMR spectroscopy. Acc Chem Res. doi:10.1021/ar300309s

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Marco Fragai
    • 1
    • 2
  • Claudio Luchinat
    • 1
    • 2
  • Giacomo Parigi
    • 1
    • 2
  • Enrico Ravera
    • 1
    • 2
  1. 1.Center for Magnetic Resonance (CERM)University of FlorenceSesto FiorentinoItaly
  2. 2.Department of ChemistryUniversity of FlorenceSesto FiorentinoItaly

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