Nature：科学家揭开朊蛋白的传染之谜
早在几十年前，研究者已经发现朊蛋白（prion）是导致疯牛病以及人类的克-雅二氏病（Cruetzfeldt-Jakob disease）的元凶。然而，时过境迁，这种观念似乎也在不断改变。新研究表明一些非致病的朊蛋白在生物学上起着重要的作用，甚至在学习和记忆中是不可或缺的成分。尽管有很多针对朊蛋白的研究，但是科学家们尚不清楚朊蛋白形成、复制和传播中许多最为基本的机制。
现在，通过研究非毒性酵母的朊蛋白，Whitehead研究所的科学家在朊蛋白中发现了一些体积小但非常关键的结构，它们对于朊蛋白的行为有着决定性的调控作用。研究成果发表在5月9日的《Nature》在线杂志上。
"这些发现为我们继续探索朊蛋白的特性提供了新的框架，而在此之前，类似研究是非常困难的。" Whitehead研究所的成员兼MIT生物学教授Susan Lindquist介绍说。他是此项研究的负责人。
原始出处:
Nature advance online publication 9 May 2007 | doi:10.1038/nature05848; Received 19 March 2007; Accepted 16 April 2007; Published online 9 May 2007
Prion recognition elements govern nucleation, strain specificity and species barriers
Peter M. Tessier1 & Susan Lindquist2
- Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
- Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Correspondence to: Susan Lindquist2 Correspondence and requests for materials should be addressed to S.L. (Email: lindquist_admin@wi.mit.edu).
Abstract
Prions are proteins that can switch to self-perpetuating, infectious conformations. The abilities of prions to replicate, form structurally distinct strains, and establish and overcome transmission barriers between species are poorly understood. We exploit surface-bound peptides to overcome complexities of investigating such problems in solution. For the yeast prion Sup35, we find that the switch to the prion state is controlled with exquisite specificity by small elements of primary sequence. Strikingly, these same sequence elements govern the formation of distinct self-perpetuating conformations (prion strains) and determine species-specific seeding activities. A Sup35 chimaera that traverses the transmission barrier between two yeast species possesses the critical sequence elements from both. Using this chimaera, we show that the influence of environment and mutations on the formation of species-specific strains is driven by selective recognition of either sequence element. Thus, critical aspects of prion conversion are enciphered by subtle differences between small, highly specific recognition elements.
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