朊病毒蛋白是錯誤一類錯誤折疊的蛋白，通常這些蛋白具有β折疊結(jié)構(gòu)域,，并能夠形成淀粉纖維狀蛋白聚集體,。這種聚集體溶解性差，并可以誘導(dǎo)周圍具有正確構(gòu)象的朊蛋白轉(zhuǎn)變成錯誤構(gòu)象,，使這種蛋白聚集體能夠擴增,，具有“傳染性”。臨床上,，很多代謝疾病和神經(jīng)退行性疾病與是由這種錯誤構(gòu)象的蛋白引發(fā)的,。近年的研究發(fā)現(xiàn),，在這些錯誤折疊的蛋白粒子中,，有輔助因子的參與,。但是輔助因子是否參與維持蛋白的錯誤構(gòu)象以及是否有助于蛋白聚集體的擴增并不清楚。
本文中,，研究者用含有輔助因子的蛋白聚集體與只含阮蛋白的蛋白聚集體作對比,。證明了去除輔助因子的蛋白聚集體在體外不具有“傳染性”，也不能誘導(dǎo)正確折疊的朊蛋白改變構(gòu)象,。研究者認(rèn)為,，朊蛋白輔助因子是組成傳染性蛋白聚集體的基本成分，它在維持聚集體構(gòu)象和誘導(dǎo)正確折疊蛋白的構(gòu)象改變中起重要作用,。
這一研究指出,，輔助因子可能在一些神經(jīng)退行性疾病的發(fā)生中扮演著重要角色，因此該研究有助于我們更好的理解這些疾病的發(fā)病機制,。（生物谷 Bioon.com ）
doi:10.1073/pnas.1206999109
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PMID:
Cofactor molecules maintain infectious conformation and restrict strain properties in purified prions
Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, and Surachai Supattapone
Prions containing misfolded prion protein (PrPSc) can be formed with cofactor molecules using the technique of serial protein misfolding cyclic amplification. However, it remains unknown whether cofactors materially participate in maintaining prion conformation and infectious properties. Here we show that withdrawal of cofactor molecules during serial propagation of purified recombinant prions caused adaptation of PrPSc structure accompanied by a reduction in specific infectivity of >105-fold, to undetectable levels, despite the ability of adapted “protein-only” PrPSc molecules to self-propagate in vitro. We also report that changing only the cofactor component of a minimal reaction substrate mixture during serial propagation induced major changes in the strain properties of an infectious recombinant prion. Moreover, propagation with only one functional cofactor (phosphatidylethanolamine) induced the conversion of three distinct strains into a single strain with unique infectious properties and PrPSc structure. Taken together, these results indicate that cofactor molecules can regulate the defining features of mammalian prions: PrPSc conformation, infectivity, and strain properties. These findings suggest that cofactor molecules likely are integral components of infectious prions.
