Prion protein peptides induce alpha-helix to beta-sheet conformational transitions.

Abstract:

:The structures of synthetic peptides corresponding to regions of putative secondary structure in the cellular prion protein PrPC were studied as models for the conformational transition that features in the formation of the pathogenic isoform, PrPSc. Transgenetic studies argue that these PrP isoforms interact during the formation of PrPSc, which involves the unfolding of one or more helices of PrPC followed by refolding into beta-sheets. PrP residues 109-122 (H1), which were predicted to be alpha-helical, form beta-sheets in aqueous buffers, while the longer peptide 104-122 (104H1) and also peptide 129-141 (H2) have coil or alpha-helical structures in solution. Both 104H1 and H2 were converted into beta-sheets upon interaction with H1, as monitored by Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy. The conversion was sequence-specific since mouse (Mo) H1, which differs from Syrian hamster (SHa) at two residues, was inefficient at converting SHa104H1 into the beta-sheet form. In buffers containing 10% acetonitrile, 104H1 was converted into the beta-sheet form by addition of as little as 1% H1. In addition, A beta 11-25 and A beta 25-35 peptides with similar physical properties to H1 were incapable of converting H2 into the beta-sheet form. How well these studies approximate the structural transitions in PrP that underlie the replication of prions remains to be established.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Nguyen J,Baldwin MA,Cohen FE,Prusiner SB

doi

10.1021/bi00013a006

subject

Has Abstract

pub_date

1995-04-04 00:00:00

pages

4186-92

issue

13

eissn

0006-2960

issn

1520-4995

journal_volume

34

pub_type

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