A new perspective on beta-sheet structures using vibrational Raman optical activity: From poly(L-lysine) to the prion protein

L.H. McColl, E.W. Blanch, A.C. Gill, A.G.O. Rhie, M.A. Ritchie, L. Hecht, Kurt Nielsen, L.D. Barron

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The vibrational Raman optical activity (ROA) spectrum of a polypeptide in a model beta-sheet conformation, that of poly(L-lysine), was measured for the first time, and the alpha-helix --> beta-sheet transition monitored as a function of temperature in H2O and D2O. Although no significant population of a disordered backbone state was detected at intermediate temperatures, some side chain bands not present in either the a-helix or beta-sheet state were observed. The observation of ROA bands in the extended amide III region assigned to beta-turns suggests that, under our experimental conditions, beta-sheet poly(L-lysine) contains up-and-down antiparallel beta-sheets based on the hairpin motif. The ROA spectrum of beta-sheet poly(L-lysine) was compared with ROA data on a number of native proteins containing different types of beta-sheet. Amide I and amide II ROA band patterns observed in beta-sheet poly(L-lySine) are different from those observed in typical beta-sheet proteins and may be characteristic of an extended flat multistranded beta-sheet, which is unlike the more irregular and twisted beta-sheet found in most proteins. However, a reduced isoform of the truncated ovine prion protein PrP94-233 that is rich in beta-sheet shows amide I and amide II ROA bands similar to those of beta-sheet poly(L-lysine), which suggests that the C-terminal domain of the prion protein is able to support unusually flat beta-sheets. A principal component analysis (PCA) that identifies protein structural types from ROA band patterns provides a useful representation of the structural relationships among the polypeptide and protein states considered in the study.
Original languageEnglish
JournalJournal of the American Chemical Society
Volume125
Issue number33
Pages (from-to)10019-10026
ISSN0002-7863
Publication statusPublished - 2003

Cite this

McColl, L. H., Blanch, E. W., Gill, A. C., Rhie, A. G. O., Ritchie, M. A., Hecht, L., Nielsen, K., & Barron, L. D. (2003). A new perspective on beta-sheet structures using vibrational Raman optical activity: From poly(L-lysine) to the prion protein. Journal of the American Chemical Society, 125(33), 10019-10026.