Journal of Biomolecular NMR

, Volume 56, Issue 4, pp 313–329 | Cite as

13C structuring shifts for the analysis of model β-hairpins and β-sheets in proteins: diagnostic shifts appear only at the cross-strand H-bonded residues

  • Irene Shu
  • Michele Scian
  • James M. Stewart
  • Brandon L. Kier
  • Niels H. Andersen
Article

Abstract

The present studies have shown that 13C=O, 13Cα and 13Cβ of H-bonded strand residues in β-hairpins provide additional probes for quantitating the extent of folding in β-hairpins and other β-sheet models. Large differences in the structuring shifts (CSDs) of these 13C sites in H-bonded versus non-H-bonded sites are observed: the differences between H-bonded and non-H-bonded sites are greater than 1.2 ppm for all three 13C probes. This prompts us to suggest that efforts to determine the extent of hairpin folding from 13C shifts should be based exclusively on the observation at the cross-strand H-bonded sites. Furthermore, the statistics suggest the 13C′ and 13CβCSDs will provide the best differentiation with 100 %-folded CSD values approaching −2.6 and +3 ppm, respectively, for the H-bonded sites. These conclusions can be extended to edge-strands of protein β-sheets. Our survey of reported 13C shifts in β-proteins indicates that some of the currently employed random coil values need to be adjusted, particularly for ionization-induced effects.

Keywords

β-hairpin β-sheet 13C chemical shift deviations Folding probes 13C statistical coil shifts 

Notes

Acknowledgments

This work was supported by the National Science Foundation (grants CHE-0650318 and -1152218).

Supplementary material

10858_2013_9749_MOESM1_ESM.pdf (648 kb)
Supplementary material 1 (PDF 648 kb)

References

  1. Andersen NH, Cort JR, Liu ZH, Sjoberg SJ, Tong H (1996) Cold denaturation of monomeric peptide helices. J Am Chem Soc 118:10309–10310CrossRefGoogle Scholar
  2. Andersen NH, Neidigh JW, Harris SM, Lee GM, Liu ZH, Tong H (1997) Extracting information from the temperature gradients of polypeptide NH chemical shifts. 1. The importance of conformational averaging. J Am Chem Soc 119:8547–8561CrossRefGoogle Scholar
  3. Andersen NH, Dyer RB, Fesinmeyer RM, Gai F, Liu ZH, Neidigh JW, Tong H (1999) Effect of hexafluoroisopropanol on the thermodynamics of peptide secondary structure formation. J Am Chem Soc 121:9879–9880CrossRefGoogle Scholar
  4. Andersen NH, Barua B, Fesinmeyer RM, Hudson FM, Lin JC, Euser A, White GW (2002) Chemical shifts, the ultimate test of peptide folding cooperativity. In: Benedetti E, Pedone C (eds) Proceedings of the 27th European peptide symposium, pp 824–825Google Scholar
  5. Andersen NH, Fesinmeyer RM, Hudson FM (2004) Analysis of peptide β-sheet models using chemical shift deviations. In: Chorev M, Sawyer KT (eds) Peptide revolution: genetics, proteomics & therapeutics. Proceedings of the 18th American peptide symposium, pp 462–463Google Scholar
  6. Andersen NH, Olsen KA, Fesinmeyer RM, Tan X, Hudson FM, Eidenschink LA, Farazi SR (2006) Minimization and optimization of designed β-hairpin folds. J Am Chem Soc 128:6101–6110CrossRefGoogle Scholar
  7. Avbelj F, Kocjan D, Baldwin RL (2004) Protein chemical shifts arising from α-helices and β-sheets depend on solvent exposure. Proc Natl Acad Sci U S A 101:17394–17397ADSCrossRefGoogle Scholar
  8. Bax A, Davis DG (1985) MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy. J Magn Reson 65:355–360Google Scholar
  9. Blanco FJ, Rivas G, Serrano L (1994) A short linear peptide that folds into a native stable β-hairpin in aqueous solution. Nat Struct Biol 1:584–590CrossRefGoogle Scholar
  10. Buck M (1998) Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins. Q Rev Biophys 31:297–355CrossRefGoogle Scholar
  11. Case DA, Dyson HJ, Wright PE (1994) Use of chemical shifts and coupling constants in nuclear magnetic resonance structural studies on peptides and proteins. Methods Enzymol 239:392–416CrossRefGoogle Scholar
  12. de Dios AC, Oldfield E (1994) Chemical-shifts of carbonyl carbons in peptides and proteins. J Am Chem Soc 116:11485–11488CrossRefGoogle Scholar
  13. de Dios AC, Pearson JG, Oldfield E (1993) Secondary and tertiary structural effects on protein NMR chemical-shifts—an Ab initio approach. Science 260:1491–1496ADSCrossRefGoogle Scholar
  14. Dyer RB, Maness SJ, Peterson ES, Franzen S, Fesinmeyer RM, Andersen NH (2004) The mechanism of β-hairpin formation. Biochemistry 43:11560–11566CrossRefGoogle Scholar
  15. Dyer RB, Maness SJ, Franzen S, Fesinmeyer RM, Olsen KA, Andersen NH (2005) Hairpin folding dynamics: the cold-denatured state is predisposed for rapid refolding. Biochemistry 44:10406–10415CrossRefGoogle Scholar
  16. Eidenschink L, Crabbe E, Andersen NH (2009a) Terminal side chain packing of a designed β-hairpin influences conformation and stability. Biopolymers 91:557–564CrossRefGoogle Scholar
  17. Eidenschink L, Kier BL, Huggins KN, Andersen NH (2009b) Very short peptides with stable folds: building on the interrelationship of Trp/Trp, Trp/cation, and Trp/backbone-amide interaction geometries. Proteins 75:308–322CrossRefGoogle Scholar
  18. Fesinmeyer RM, Hudson FM, Andersen NH (2004) Enhanced hairpin stability through loop design: the case of the protein G B1 domain hairpin. J Am Chem Soc 126:7238–7243CrossRefGoogle Scholar
  19. Fesinmeyer RM, Hudson FM, Olsen KA, White GW, Euser A, Andersen NH (2005a) Chemical shifts provide fold populations and register of β-hairpins and β-sheets. J Biomol NMR 33:213–231CrossRefGoogle Scholar
  20. Fesinmeyer RM, Peterson ES, Dyer RB, Andersen NH (2005b) Studies of helix fraying and solvation using 13C′ isotopomers. Protein Sci 14:2324–2332CrossRefGoogle Scholar
  21. Griffiths-Jones SR, Maynard AJ, Searle MS (1999) Dissecting the stability of a β-hairpin peptide that folds in water: NMR and molecular dynamics analysis of the β-turn and β-strand contributions to folding. J Mol Biol 292:1051–1069CrossRefGoogle Scholar
  22. Hudson FM, Andersen NH (2006) Measuring cooperativity in the formation of a three-stranded β-sheet (double hairpin). Biopolymers 83:424–433CrossRefGoogle Scholar
  23. Huggins KNL, Andersen NH (2010) Hairpin peptide inhibitors of amyloid fibrils formation. In: Lankinen H (eds) Chemistry of peptides in life science, technology and medicine. Proceedings of the 30th European peptide symposium, pp 590–591Google Scholar
  24. Iwadate M, Asakura T, Williamson MP (1999) Cα and Cβ carbon-13 chemical shifts in proteins from an empirical database. J Biomol NMR 13:199–211CrossRefGoogle Scholar
  25. Kier BL, Andersen NH (2008) Probing the lower size limit for protein-like fold stability: ten-residue microproteins with specific, rigid structures in water. J Am Chem Soc 130:14675–14683CrossRefGoogle Scholar
  26. Kier BL, Andersen NH (2009) Short, hyperstable β-sheets without turns. Biopolym Peptide Sci 92:311Google Scholar
  27. Kier BL, Shu I, Eidenschink LA, Andersen NH (2010) Stabilizing capping motif for beta-hairpins and sheets. Proc Natl Acad Sci U S A 107:10466–10471ADSCrossRefGoogle Scholar
  28. Kobayashi N, Endo S, Munekata E (1993) Conformational study on the IgG binding domain of protein G. In: Peptide chemistry, pp 278–281Google Scholar
  29. Luo P, Baldwin RL (1997) Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. Biochemistry 36:8413–8421CrossRefGoogle Scholar
  30. Maynard AJ, Sharman GJ, Searle MS (1998) Origin of β-hairpin stability in solution: structural and thermodynamic analysis of the folding of model peptide supports hydrophobic stabilization in water. J Am Chem Soc 120:1996–2007CrossRefGoogle Scholar
  31. Mehrnejad F, Naderi-Manesh H, Ranjbar B (2007) The structural properties of magainin in water, TFE/water, and aqueous urea solutions: molecular dynamics simulations. Proteins 67:931–940CrossRefGoogle Scholar
  32. Olsen KA, Fesinmeyer RM, Stewart JM, Andersen NH (2005) Hairpin folding rates reflect mutations within and remote from the turn region. Proc Natl Acad Sci U S A 102:15483–15487ADSCrossRefGoogle Scholar
  33. Piotto M, Saudek V, Sklenar V (1992) Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J Biomol NMR 2:661–665CrossRefGoogle Scholar
  34. Saito H (1986) Conformation-dependent C-13 chemical-shifts—a new means of conformational characterization as obtained by high-resolution solid-state C-13 Nmr. Magn Reson Chem 24:835–852CrossRefGoogle Scholar
  35. Santiveri CM, Rico M, Jimenez MA (2001) 13C(alpha) and 13C(beta) chemical shifts as a tool to delineate beta-hairpin structures in peptides. J Biomol NMR 19:331–345CrossRefGoogle Scholar
  36. Santiveri CM, Pantoja-Uceda D, Rico M, Jimenez MA (2005) β-hairpin formation in aqueous solution and in the presence of trifluoroethanol: a (1)H and (13)C nuclear magnetic resonance conformational study of designed peptides. Biopolymers 79:150–162CrossRefGoogle Scholar
  37. Schenck HL, Gellman SH (1998) Use of a designed triple-stranded antiparallel β-sheet to probe β-sheet cooperativity in aqueous solution. J Am Chem Soc 120:4869–4870CrossRefGoogle Scholar
  38. Schwarzinger S, Kroon GJ, Foss TR, Wright PE, Dyson HJ (2000) Random coil chemical shifts in acidic 8 M urea: implementation of random coil shift data in NMRView. J Biomol NMR 18:43–48CrossRefGoogle Scholar
  39. Schwarzinger S, Kroon GJ, Foss TR, Chung J, Wright PE, Dyson HJ (2001) Sequence-dependent correction of random coil NMR chemical shifts. J Am Chem Soc 123:2970–2978CrossRefGoogle Scholar
  40. Sharman GJ, Griffiths-Jones SR, Jourdan M, Searle MS (2001) Effects of amino acid phi, psi propensities and secondary structure interactions in modulating Hα chemical shifts in peptide and protein β-sheet. J Am Chem Soc 123:12318–12324CrossRefGoogle Scholar
  41. Shu I, Stewart JM, Scian M, Kier BL, Andersen NH (2011) β-Sheet 13C structuring shifts appear only at the H-bonded sites of hairpins. J Am Chem Soc 133:1196–1199CrossRefGoogle Scholar
  42. Sibanda BL, Thornton JM (1991) Conformation of β-hairpins in protein structures: classification and diversity in homologous structures. Methods Enzymol 202:59–82CrossRefGoogle Scholar
  43. Spera S, Bax A (1991) Empirical correlation between protein backbone conformation and C-Alpha and C-Beta C-13 nuclear-magnetic-resonance chemical-shifts. J Am Chem Soc 113:5490–5492CrossRefGoogle Scholar
  44. Tatko CD, Waters ML (2003) The geometry and efficacy of cation-pi interactions in a diagonal position of a designed β-hairpin. Protein Sci 12:2443–2452CrossRefGoogle Scholar
  45. Vila JA, Scheraga HA (2008) Factors affecting the use of 13C(alpha) chemical shifts to determine, refine, and validate protein structures. Proteins 71:641–654CrossRefGoogle Scholar
  46. Vila JA, Arnautova YA, Scheraga HA (2008) Use of 13C(alpha) chemical shifts for accurate determination of β-sheet structures in solution. Proc Natl Acad Sci U S A 105:1891–1896ADSCrossRefGoogle Scholar
  47. Vuister GW, Bax A (1992) Measurement of two-bond JCOH alpha coupling constants in proteins uniformly enriched with 13C. J Biomol NMR 2:401–405CrossRefGoogle Scholar
  48. Wishart DS, Sykes BD (1994) The 13C chemical-shift index: a simple method for the identification of protein secondary structure using 13C chemical-shift data. J Biomol NMR 4:171–180CrossRefGoogle Scholar
  49. Wishart DS, Sykes BD, Richards FM (1991) Relationship between nuclear magnetic resonance chemical shift and protein secondary structure. J Mol Biol 222:311–333CrossRefGoogle Scholar
  50. Wishart DS, Bigam CG, Holm A, Hodges RS, Sykes BD (1995) 1H, 13C and 15 N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. J Biomol NMR 5:67–81CrossRefGoogle Scholar
  51. Xu XP, Case DA (2002) Probing multiple effects on 15 N, 13C alpha, 13C beta, and 13C′ chemical shifts in peptides using density functional theory. Biopolymers 65:408–423CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Irene Shu
    • 1
  • Michele Scian
    • 1
  • James M. Stewart
    • 1
  • Brandon L. Kier
    • 1
  • Niels H. Andersen
    • 1
  1. 1.Department of ChemistryUniversity of WashingtonSeattleUSA

Personalised recommendations