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.
Fold Des
; 3(5): 313-20, 1998.
Article
em En
| MEDLINE
| ID: mdl-9806936
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Príons
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Fold Des
Ano de publicação:
1998
Tipo de documento:
Article