NR AKTF
AU Sharman,G.J.; Kenward,N.; Williams,H.E.; Landon,M.; Mayer,R.J.; Searle,M.S.
TI Prion protein fragments spanning helix 1 and both strands of beta sheet (residues 125-170) show evidence for predominantly helical propensity by CD and NMR
QU Folding and Design 1998; 3(5): 313-20
PT journal article
AB BACKGROUND: Transmissible spongiform encephalopathies are a group of neurodegenerative disorders of man and animals that are believed to be caused by an alpha-helical to beta-sheet conformational change in the prion protein, PrP. Recently determined NMR structures of recombinant PrP (residues 121-231 and 90-231) have identified a short two-stranded anti-parallel beta sheet in the normal cellular form of the protein (PrPc). This beta sheet has been suggested to be involved in seeding the conformational transition to the disease-associated form (PrPsc) via a partially unfolded intermediate state. RESULTS: We describe CD and NMR studies of three peptides (125-170, 142-170 and 156-170) that span the beta-sheet and helix 1 region of PrP, forming a large part of the putative PrPsc-PrPc binding site that has been proposed to be important for self-seeding replication of PrPsc. The data suggest that all three peptides in water have predominantly helical propensities, which are enhanced in aqueous methanol (as judged by deviations from random-coil Halpha chemical shifts and 3JHalpha-NH values). Although the helical propensity is most marked in the region corresponding to helix 1 (144-154), it is also apparent for residues spanning the two beta-strand sequences. CONCLUSIONS: We have attempted to model the conformational properties of a partially unfolded state of PrP using peptide fragments spanning the region 125-170. We find no evidence in the sequence for any intrinsic conformational preference for the formation of extended beta-like structure that might be involved in promoting the PrPc-PrPsc conformational transition.
MH Animal; Circular Dichroism; Human; Magnetic Resonance Spectroscopy; Peptide Fragments/*chemistry; Prions/*chemistry; Protein Conformation; Support, Non-U.S. Gov't; Water/chemistry
AD Department of Chemistry University of Nottingham University Park Nottingham, NG7 2RD, UK
SP englisch
PO England