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摘要 : 脂质穿过膜双层的转位(被称为翻转)是维持脂质非对称性所必需的,也是信号传导和囊泡形成等过程所要求的。

 脂质穿过膜双层的转位(被称为翻转)是维持脂质非对称性所必需的,也是信号传导和囊泡形成等过程所要求的。嵌入在膜中的脂质(含有大型极性头基)的翻转是缓慢的,从能量角度来讲也是不利的。这一过程由翻转酶催化,其机制目前尚不知道。本文作者获得了ABC transporter PglK的X-射线晶体结构,该物质在Campylobacter jejuni中、在向内和向外的状态下帮助“脂联寡糖”(LLO)的翻转。这些结构和随后的生物化学实验支持一个不同寻常的机制,在其中LLO的 “聚戊烯基”尾巴仍然部分嵌入在脂质双层中,“焦磷酸盐-寡糖”头基在ATP被水解之后翻转到了向外的空腔内。


Structure and mechanism of an active lipid-linked oligosaccharide flippase


The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N-linked protein glycosylation. In Campylobacter jejuni, this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid-linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward- and outward-facing conformations in vitro, but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters.

来源: Nature 浏览次数:141


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