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Publication Abstract from PubMed

The pathogenesis of prion diseases is associated with the conformational conversion of normal, predominantly alpha-helical prion protein (PrPC) into a pathogenic form that is enriched in beta-sheet (PrPSc). Several PrPC crystal structures have revealed beta1-mediated intermolecular sheets, suggesting that the beta1 strand may contribute to a possible initiation site for beta-sheet mediated PrPSc propagation. This beta1 strand contains the polymorphic residue 129 which influences disease susceptibility and phenotype. To investigate the effect of the residue 129 polymorphism on the conformation of amyloid-like continuous beta-sheets formed by beta1, crystal structures of beta1 peptides containing each of the polymorphic residues were determined. To probe the conformational influence of the peptide construct design, four different lengths of beta1 peptides were studied. From the twelve peptides studied, eleven yielded crystal structures ranging in resolution from 0.9 A to 1.4 A. This ensemble of beta1 crystal structures reveals conformational differences which are influenced by both the nature of the polymorphic residue and the extent of the peptide construct, indicating that comprehensive studies which vary peptide constructs are a more rigorous approach to surveying conformational possibilities.

Crystal structures of polymorphic prion protein beta1 peptides reveal variable steric zipper conformations.,Yu L, Lee SJ, Yee VC Biochemistry. 2015 May 15. PMID:25978088^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.