早在幾十年前，研究者已經(jīng)發(fā)現(xiàn)朊蛋白（prion）是導(dǎo)致瘋牛病以及人類的克-雅二氏?。–ruetzfeldt-Jakob disease）的元兇,。然而，時(shí)過(guò)境遷,，這種觀念似乎也在不斷改變,。新研究表明一些非致病的朊蛋白在生物學(xué)上起著重要的作用，甚至在學(xué)習(xí)和記憶中是不可或缺的成分,。盡管有很多針對(duì)朊蛋白的研究,，但是科學(xué)家們尚不清楚朊蛋白形成、復(fù)制和傳播中許多最為基本的機(jī)制,。
現(xiàn)在,，通過(guò)研究非毒性酵母的朊蛋白，Whitehead研究所的科學(xué)家在朊蛋白中發(fā)現(xiàn)了一些體積小但非常關(guān)鍵的結(jié)構(gòu),，它們對(duì)于朊蛋白的行為有著決定性的調(diào)控作用,。研究成果發(fā)表在5月9日的《Nature》在線雜志上。
"這些發(fā)現(xiàn)為我們繼續(xù)探索朊蛋白的特性提供了新的框架,，而在此之前,，類似研究是非常困難的,。" Whitehead研究所的成員兼MIT生物學(xué)教授Susan Lindquist介紹說(shuō)。他是此項(xiàng)研究的負(fù)責(zé)人,。
原始出處:
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: [email protected]).
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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.
