The structure of Yersinia pestis V-antigen, an essential virulence factor and mediator of immunity against plague
The structure of Yersinia pestis V-antigen, an essential virulence factor and mediator of immunity against plague
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DOI：
10.1016/j.str.2004.01.010
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发表时间：
2004-02-01
期刊：
影响因子：
5.7
通讯作者：
Waugh, DS
中科院分区：
文献类型：
--
作者：
Derewenda, U;Mateja, A;Waugh, DS
LcrV蛋白(V抗原)是鼠疫病原体鼠疫耶尔森氏菌中的一种多功能毒力因子。LcrV通过III型分泌系统调节细胞毒效应蛋白从细菌到细胞质的转运，具有自身的抗宿主活性，也是一种主动和被动的抗病介质。虽然为了更好地了解该蛋白在发病机制中的作用，人们一直在积极寻找该蛋白的晶体结构，但野生型LcrV被发现对结晶具有顽固性。我们采用表面熵还原诱变策略获得了衍射率为2.2埃的LCrV晶体，并确定了它的结构。改进的模型揭示了一个具有新折叠的哑铃状分子，其中包括一个意想不到的螺旋线圈基序，并为探索这一重要毒力决定因素的结构-功能关系提供了详细的三维路线图。
The LcrV protein (V-antigen) is a multifunctional virulence factor in Yersinia pestis, the causative agent of plague. LcrV regulates the translocation of cytotoxic effector proteins from the bacterium into the cytosol of mammalian cells via a type III secretion system, possesses antihost activities of its own, and is also an active and passive mediator of resistance to disease. Although a crystal structure of this protein has been actively sought for better understanding of its role in pathogenesis, the wild-type LcrV was found to be recalcitrant to crystallization. We employed a surface entropy reduction mutagenesis strategy to obtain crystals of LcrV that diffract to 2.2 Angstrom and determined its structure. The refined model reveals a dumbbell-like molecule with a novel fold that includes an unexpected coiled-coil motif, and provides a detailed three-dimensional roadmap for exploring structure-function relationships in this essential virulence determinant.