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  • 标题:X-ray fibre diffraction analysis of assemblies formed by prion-related peptides: Polymorphism of the heterodimer interface between PrPC and PrPSc
  • 本地全文:下载
  • 作者:Hideyo Inouye ; Daniel A. Kirschner
  • 期刊名称:Fibre Diffraction Review : the CCP13 Newsletter ; Software Development for Fibre Diffraction (Formerly The CCP13 Newsletter)
  • 印刷版ISSN:1463-8401
  • 电子版ISSN:1463-8401
  • 出版年度:2003
  • 卷号:11
  • 出版社:CCLRC Daresbury Laboratory
  • 摘要:The molecular mechanism in prion diseases involves structural alteration of the non-infectious cellular isoform (PrPC) to the infectious, scrapie isoform (PrPSc). The structural transition is thought to involve a binding interface between the two isoforms in their N-terminal domains. Because prions and prion-related peptides can form amyloid-like fibrillar assemblies, we have used X-ray fibre diffraction to study the structure of the binding interface in synthetic peptides that have sequence similarity with the prion protein (PrP). Our previous studies show that the alanine-rich peptides PrP106-122 and PrP109-122 form slab-like structures that are stacked as one-dimensional lattices having cumulative disorder. The unit cell is a fourstranded β-sheet with the chains directed along the stacking direction. Neighboring β-sheets are quarterstaggered (like in β silk). Electron density projections indicate that the peptides form a reverse turn with the larger residues in the N-terminal domain distinguishable from the alanine-rich C-terminal domain. This reverse turn accounts for the 33 Å-length of β chains (or slab thickness) as measured from the low-angle scattering. In this report, we considered three different inter-molecular packings for the reverse turn molecules: i.e., anti-parallel, parallel, and staggered. The staggered arrangement gave the best agreement between the observed and calculated X-ray intensities. From the molecular model we suggest that the autocatalytic replication of prions may involve hydrogen-bonding between intermolecular antiparallel β chains of the alanine-rich domains at the binding interface between PrPC and PrPSc.
  • 关键词:Prion; amyloid; X-ray diffraction; reverse turn; beta-pleated sheet
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