生物谷報(bào)道：阿爾茨海默氏癥和帕金森氏癥等神經(jīng)退化疾病與淀粉狀纖絲在大腦中的沉積有關(guān),。纖絲在結(jié)構(gòu)上非常統(tǒng)一，看看產(chǎn)生它們的蛋白的多樣性就知道了?，F(xiàn)在，Sawaya等人識(shí)別出了來(lái)自很多不同淀粉狀疾病的能夠形成纖絲的短肽,，并且獲得了由它們當(dāng)中的13種所形成的晶體的原子結(jié)構(gòu),。迄今分析過(guò)的所有這些肽,，都通過(guò)形成“steric zipper”的變種而進(jìn)行自組裝。“steric zipper”是在酵母鋸蛋白Sup 35中首次發(fā)現(xiàn)的一種結(jié)構(gòu)特征,。這種“拉鏈”可能是淀粉狀纖絲強(qiáng)度的關(guān)鍵,，是治療干預(yù)的首要目標(biāo)。
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: [email protected]).
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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.
