Journal of Biomolecular NMR

, Volume 33, Issue 4, pp 213–231 | Cite as

Chemical Shifts Provide Fold Populations and Register of β Hairpins and β Sheets

  • R. Matthew Fesinmeyer
  • F. Michael Hudson
  • Katherine A. Olsen
  • George W. N. White
  • Anna Euser
  • Niels H. Andersen
Article

Abstract

A detailed analysis of peptide backbone amide (HN) and Hα chemical shifts reveals a consistent pattern for β hairpins and three-stranded β sheets. The Hα’s at non-hydrogen-bonded strand positions are inwardly directed and shifted downfield ~1 ppm due largely to an anisotropy contribution from the cross-strand amide function. The secondary structure associated Hα shift deviations for the H-bonded strand positions are also positive but much smaller (0.1–0.3 ppm) and the turn residues display negative Hα chemical shift deviations (CSDs). The pattern of (HN) shift deviations is an even better indicator of both hairpin formation and register, with the cross-strand H-bonded sites shifted downfield (also by ~1 ppm) and with diagnostic values for the first turn residue and the first strand position following the turn. These empirical observations, initially made for [2:2]/[2:4]-type-I' and -II' hairpins, are rationalized and can be extended to the analysis of other turns, hairpin classes ([3:5], [4:4]/[4:6]), and three-stranded peptide β-sheet models. The Hα’s at non-hydrogen-bonded sites and (HN)’s in the intervening H-bonded sites provide the largest and most dependable measures of hairpin structuring and can be used for melting studies; however the intrinsic temperature dependence of (HN) shifts deviations needs to reflect the extent of solvent sequestration in the folded state. Several observations made in the course of this study provide insights into β-sheet folding mechanisms: (1) The magnitude of the (HN) shifts suggests that the cross-strand H-bonds in peptide hairpins are as short as those in protein β sheets. (2) Even L-Pro-Gly turns, which are frequently used in unfolded controls for hairpin peptides, can support hairpin populations in aqueous fluoroalcohol media. (3) The good correlation between hairpin population estimates from cross-strand H-bonded (HN) shift deviations, Hα shift deviations, and structuring shifts at the turn locus implies that hairpin folding transitions approximate two-state behavior.

Keywords

chemical shift deviations CSD hairpin fold population hairpin register turn signatures two-state folding 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

supp1.pdf (336 kb)
Supplementary material
supp2.pdf (791 kb)
Supplementary material
supp1.doc (298 kb)
Supplementary material
supp2.doc (1.4 mb)
Supplementary material

References

  1. Andersen, N.H., Brodsky, Y., Neidigh, J.W., Prickett, K.S. 2002Bioorg. Med. Chem.107985Google Scholar
  2. Andersen, N.H., Cort, J.R., Liu, Z., Sjoberg, S.J., Tong, H. 1996J. Am. Chem. Soc.1181030910310Google Scholar
  3. Andersen, N.H., Dyer, R.B., Fesinmeyer, R.M., Gai, F., Liu, Z., Neidigh, J.W., Tong, H. 1999J. Am. Chem. Soc.12198799880CrossRefGoogle Scholar
  4. Andersen, N.H., Neidigh, J.W., Harris, S.M., Lee, G.M., Liu, Z., Tong, H. 1997J. Am. Chem. Soc.11985478561CrossRefGoogle Scholar
  5. Blanco, F.J., Jiménez, M.A., Herranz, J., Rico, M., Santoro, J., Nieto, J.L. 1993J. Am. Chem. Soc.11558875888CrossRefGoogle Scholar
  6. Blanco, F.J., Rivas, G., Serrano, L. 1994Nat. Struct. Biol.1584590CrossRefGoogle Scholar
  7. Blanco, F.J., Serrano, L. 1995Eur. J. Biochem.230634649CrossRefGoogle Scholar
  8. Blandl, T., Cochran, A.G., Skelton, N.J. 2003Protein Sci.12237247CrossRefGoogle Scholar
  9. Bradley, E.K., Thomason, J.F., Cohen, F.E., Kosen, P.A., Kuntz, I.D. 1990J. Mol. Biol.215607622Google Scholar
  10. Brown, J.E., Klee, W.A. 1971Biochemistry10470476CrossRefGoogle Scholar
  11. Chen, P.-Y., Lin, C.-K., Lee, C.-T., Jan, H., Chan, S.I. 2001Protein Sci.1017941800Google Scholar
  12. Ciani, B., Jourdan, M., Searle, M.S. 2003J. Am. Chem. Soc.12590389047CrossRefGoogle Scholar
  13. Cierpicki, T., Otlewski, J. 2001J. Biomol. NMR21249261CrossRefGoogle Scholar
  14. Cochran, A.G., Skelton, N.J., Starovasnik, M.A. 2001Proc. Natl. Acad. Sci. USA9855785583CrossRefGoogle Scholar
  15. Cort, J.R., Liu, Z., Lee, G.M., Harris, S.M., Prickett, K.S., Gaeta, L.S.L., Andersen, N.H. 1994Biochem. Biophys. Res. Commun.20410881095CrossRefGoogle Scholar
  16. Cox, J.P.H., Evans, P.A., Packman, L.C., Williams, D.H., Woolfson, D.N. 1993J. Mol. Biol.234483492CrossRefGoogle Scholar
  17. Alba, E., Jiménez, M.A., Rico, M., Nieto, J.L. 1996Fold. Des.1133144Google Scholar
  18. Alba, E., Rico, M., Jiménez, M.A. 1999Protein Sci.822342244Google Scholar
  19. Doig, A.J., Baldwin, R.L. 1995Protein Sci.413251336Google Scholar
  20. Dyer, R.B., Manas, E.S., Peterson, E.S., Franzen, S., Fesinmeyer, R.M., Andersen, N.H. 2004Biochemistry431156011566CrossRefGoogle Scholar
  21. Dyer, R.B., Maness, S.J., Franzen, S., Fesinmeyer, R.M., Olsen, K.A., Andersen, N.H. 2005Biochemistry441040610415CrossRefGoogle Scholar
  22. Espinosa, J.F., Gellman, S.H. 2000Angew. Chem. Int. Ed.3923302333CrossRefGoogle Scholar
  23. Espinosa, J.F., Muñoz, V., Gellman, S.H. 2001J. Mol. Biol.306397402CrossRefGoogle Scholar
  24. Espinosa, J.F., Syud, F.A., Gellman, S.H. 2002Protein Sci.1114921505CrossRefGoogle Scholar
  25. Fesinmeyer, R.M., Hudson, F.M., Andersen, N.H. 2004J. Am. Chem. Soc.12672387243CrossRefGoogle Scholar
  26. Frishman, D., Argos, P. 1995Proteins23566579CrossRefGoogle Scholar
  27. Gibbs, A.C., Bjorndahl, T.C., Hodges, R.S., Wishart, D.S. 2002J. Am. Chem. Soc.12412031213CrossRefGoogle Scholar
  28. Griffiths-Jones, S.R., Maynard, A.J., Searle, M.S. 1999J. Mol. Biol.29210511069CrossRefGoogle Scholar
  29. Griffiths-Jones, S.R., Searle, M.S. 2000J. Am. Chem. Soc.12283508356CrossRefGoogle Scholar
  30. Honda, S., Kobayashi, N., Munekata, E. 2000J. Mol. Biol.295269278CrossRefGoogle Scholar
  31. Hughes, R.M., Waters, M.L. 2005J. Am. Chem. Soc.12765186519Google Scholar
  32. Karle, I.L., Awasthi, S.K., Balaram, P. 1996Proc. Natl. Acad. Sci. USA9381898193CrossRefGoogle Scholar
  33. Kiehna, S.E., Waters, M.L. 2003Protein Sci.1226572667CrossRefGoogle Scholar
  34. Kobayashi, N., Endo, S. and Munekata, E. (1993) Peptide Chem., 278–280Google Scholar
  35. Lee, G.M., Chen, C., Marschner, T.M., Andersen, N.H. 1994FEBS Lett.355140146CrossRefGoogle Scholar
  36. López Paz, M., Lacroix, E., Ramírez-Alvarado, M., Serrano, L. 2001J. Mol. Biol.312229246Google Scholar
  37. Maynard, A.J., Sharman, G.J., Searle, M.S. 1998J. Am. Chem. Soc.12019962007CrossRefGoogle Scholar
  38. Merutka, G., Dyson, H.J., Wright, P.E. 1995J. Biomol. NMR51424Google Scholar
  39. Muñoz, V., Thompson, P.A., Hofrichter, J., Eaton, W.A. 1997Nature390196199Google Scholar
  40. Osapay, K., Case, D.A. 1991J. Am. Chem. Soc.11394369444CrossRefGoogle Scholar
  41. Osapay, K., Case, D.A. 1994J. Biomol. NMR4215230Google Scholar
  42. Piotto, M., Saudek, V., Sklenar, V. 1992J. Biomol. NMR2661665CrossRefGoogle Scholar
  43. Ramírez-Alvarado, M., Blanco, F.J., Niemann, H., Serrano, L. 1997J. Mol. Biol.273898912Google Scholar
  44. Ramírez-Alvarado, M., Blanco, F.J., Serrano, L. 1996Nat. Struct. Biol.3604612Google Scholar
  45. Roe, D.R., Hornack, V., Simmerling, C. 2005J. Mol. Biol.352370381CrossRefGoogle Scholar
  46. Santiveri, C.M., Rico, M., Jiménez, M.A. 2001J. Biomol. NMR19331345CrossRefGoogle Scholar
  47. Santiveri, C.M., Rico, M., Jiménez, M.A., Pastor, M.T., Pérez-Payá, E. 2003J. Pept. Res.61177188CrossRefGoogle Scholar
  48. Santiveri, C.M., Santoro, J., Rico, M., Jiménez, M.A. 2002J. Am. Chem. Soc.1241490314909CrossRefGoogle Scholar
  49. Santiveri, C.M., Santoro, J., Rico, M., Jiménez, M.A. 2004Protein Sci.1311341147CrossRefGoogle Scholar
  50. Schenck, H., Gellman, S. 1998J. Am. Chem. Soc.12048694870CrossRefGoogle Scholar
  51. Schwarzinger, S., Kroon, G.J.A., Foss, T.R., Wright, P.E., Dyson, H.J. 2000J. Biomol. NMR184348CrossRefGoogle Scholar
  52. Searle, M.S. 2001J. Chem. Soc. Perkin Trans.210111020Google Scholar
  53. Searle, M.S., Williams, D.H., Packman, L.C. 1995Nat. Struct. Biol.29991006CrossRefGoogle Scholar
  54. Sharman, G.J., Griffiths-Jones, S.R., Jourdan, M., Searle, M.S. 2001J. Am. Chem. Soc.1231231812324CrossRefGoogle Scholar
  55. Sharman, G.J., Searle, M.S. 1998J. Am. Chem. Soc.12052915300CrossRefGoogle Scholar
  56. Sibanda, B.L., Thornton, J.M. 1991Methods Enzymol.2025982Google Scholar
  57. Syud, F.A., Espinosa, J.F., Gellman, S.H. 1999J. Am. Chem. Soc.1211157711578CrossRefGoogle Scholar
  58. Syud, F.A., Stanger, H.E., Gellman, S.H. 2001J. Am. Chem. Soc.12386678677CrossRefGoogle Scholar
  59. Syud, F.A., Stanger, H.E., Mortell, H.S., Espinosa, J.F., Fisk, J.D., Fry, C.G., Gellman, S.H. 2003J. Mol. Bio.326553568Google Scholar
  60. Tatko, C.D., Waters, M.L. 2003Protein Sci1224432452CrossRefGoogle Scholar
  61. Tatko, C.D., Waters, M.L. 2004Protein Sci.1325152522CrossRefGoogle Scholar
  62. Trabi, M., Schirra, H.J., Craik, D.J. 2001Biochemistry4042114221CrossRefGoogle Scholar
  63. Wagner, G., Pardi, A., Wuthrich, K. 1983J. Am. Chem. Soc.10559485949CrossRefGoogle Scholar
  64. Wishart, D.S., Bigam, C.G., Holm, A., Hodges, R.S., Sykes, B.D. 1995J. Biomol. NMR56781Google Scholar
  65. Wishart, D.S., Sykes, B.D. 1994Methods Enzymol.239363392Google Scholar
  66. Wishart, D.S., Sykes, B.D., Richards, F.M. 1991J. Mol. Bio.222311333Google Scholar
  67. Xu, X.P., Case, D.A. 2001J. Biomol. NMR21321333CrossRefGoogle Scholar
  68. Xu, X.P., Case, D.A. 2002Biopolymers65408423Google Scholar
  69. Xu, Y., Oyola, R., Gai, F. 2003J. Am. Chem. Soc.1251538815394Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • R. Matthew Fesinmeyer
    • 1
  • F. Michael Hudson
    • 1
  • Katherine A. Olsen
    • 1
  • George W. N. White
    • 1
    • 2
  • Anna Euser
    • 1
  • Niels H. Andersen
    • 1
  1. 1.Department of ChemistryUniversity of WashingtonSeattleUSA
  2. 2.Rotation student in the University of Washington Biomolecular Structure & Design programUSA

Personalised recommendations