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.