Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion
Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion
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DOI：
10.1038/35102073
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发表时间：
2001-11-01
期刊：
影响因子：
64.8
通讯作者：
Galán, JE
中科院分区：
文献类型：
--
作者：
Stebbins, CE;Galán, JE
许多细菌病原体使用III型蛋白分泌系统将毒力效应蛋白直接递送到宿主细胞胞质溶胶中，在那里它们调节细胞过程（1，2）。几种这样的效应蛋白的有效易位的要求是特异性胞质分子伴侣的结合，其通常与毒力因子中的离散结构域相互作用（3，4，5）。我们在这里报告的晶体结构在1.9埃分辨率的伴侣蛋白结合结构域的沙门氏菌效应蛋白SptP与其同源伴侣SicP。该结构揭示了该结构域保持在延伸的未折叠构象中，该构象缠绕在三个连续的伴侣分子周围。来自两个不同SptP分子的短片段由分子伴侣并置，在那里它们跨越疏水界面二聚化。这些结果意味着与III型分泌系统相关的分子伴侣将其底物保持在分泌能力状态，该状态能够接合分泌机器以未折叠或部分折叠的方式穿过III型装置。
Many bacterial pathogens use a type III protein secretion system to deliver virulence effector proteins directly into the host cell cytosol, where they modulate cellular processes(1,2). A requirement for the effective translocation of several such effector proteins is the binding of specific cytosolic chaperones, which typically interact with discrete domains in the virulence factors(3,4,5). We report here the crystal structure at 1.9 Angstrom resolution of the chaperone-binding domain of the Salmonella effector protein SptP with its cognate chaperone SicP. The structure reveals that this domain is maintained in an extended, unfolded conformation that is wound around three successive chaperone molecules. Short segments from two different SptP molecules are juxtaposed by the chaperones, where they dimerize across a hydrophobic interface. These results imply that the chaperones associated with the type III secretion system maintain their substrates in a secretion-competent state that is capable of engaging the secretion machinery to travel through the type III apparatus in an unfolded or partially folded manner.