Nature：能够形成淀粉状纤丝的短肽及其晶体结构
生物谷报道：阿尔茨海默氏症和帕金森氏症等神经退化疾病与淀粉状纤丝在大脑中的沉积有关。纤丝在结构上非常统一，看看产生它们的蛋白的多样性就知道了。现在，Sawaya等人识别出了来自很多不同淀粉状疾病的能够形成纤丝的短肽，并且获得了由它们当中的13种所形成的晶体的原子结构。迄今分析过的所有这些肽，都通过形成“steric zipper”的变种而进行自组装。“steric zipper”是在酵母锯蛋白Sup 35中首次发现的一种结构特征。这种“拉链”可能是淀粉状纤丝强度的关键，是治疗干预的首要目标。
英文原文：
Article
Nature 447, 453-457 (24 May 2007) | doi:10.1038/nature05695; Received 30 November 2006; Accepted 19 February 2007; Published online 29 April 2007
Atomic structures of amyloid cross-
spines reveal varied steric zippers
Michael R. Sawaya1, Shilpa Sambashivan1, Rebecca Nelson1, Magdalena I. Ivanova1, Stuart A. Sievers1, Marcin I. Apostol1, Michael J. Thompson1, Melinda Balbirnie1, Jed J. W. Wiltzius1, Heather T. McFarlane1, Anders Ø. Madsen2,3, Christian Riekel3 & David Eisenberg1
- Howard Hughes Medical Institute, UCLA-DOE Institute of Genomics and Proteomics, Los Angeles, California 90095-1570, USA
- Centre for Crystallographic Studies, Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 KBH, Denmark
- European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble Cedex, France
Correspondence to: David Eisenberg1 Correspondence and requests for materials should be addressed to D.E. (Email: david@mbi.ucla.edu).
Abstract
Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-
spine. The atomic architecture of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein Sup35, was recently revealed by X-ray microcrystallography. It is a pair of -sheets, with the facing side chains of the two sheets interdigitated in a dry 'steric zipper'. Here we report some 30 other segments from fibril-forming proteins that form amyloid-like fibrils, microcrystals, or usually both. These include segments from the Alzheimer's amyloid- and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, 
-synuclein and 2-microglobulin, suggesting that common structural features are shared by amyloid diseases at the molecular level. Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains.
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