Structures of amyloid fibrils formed by the prion protein derived peptides PrP(244-249) and PrP(245-250) - PubMed (original) (raw)

. 2012 Nov;180(2):290-302.

doi: 10.1016/j.jsb.2012.08.002. Epub 2012 Aug 21.

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Structures of amyloid fibrils formed by the prion protein derived peptides PrP(244-249) and PrP(245-250)

Jason Yau et al. J Struct Biol. 2012 Nov.

Abstract

While the formation of amyloid fibrils from diverse peptide and protein sequences is well established, the molecular determinants of structure and assembly are not well understood. In particular, the relationship between amino acid sequence and the type of internal steric zipper packing adopted in amyloid fibrils has not been established. Here we report the structures of two cytotoxic amyloid peptides derived from the mammalian prion protein, PrP(244-249) and PrP(245-250), determined using solid state NMR. While the amino acid composition of these two hexapeptides is very similar (ISFLIF and SFLIFL), the intermolecular interactions that give rise to the intersheet packing within the fibrils differ significantly. PrP(245-250) adopts a class 1 steric zipper, with parallel sheets stacked in an antiparallel face to face arrangement, stabilized by N- to C-terminal salt bridges. PrP(244-249), by contrast, forms two different intersheet interfaces within amyloid fibrils, with parallel opposing sheets in either a face to face (class 3) or face to back (class 2) arrangement. The fibrils formed by this peptide are primarily stabilized by close packing of the hydrophobic side chains, with contributions from side-chain to backbone hydrogen bonding (class 2 only). Thus, the structures presented here provide new insight into the relationship between amino acid sequence and the types of interactions stabilizing amyloid fibrils.

Copyright © 2012 Elsevier Inc. All rights reserved.

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