The crystal structures of the Salmonella type III secretion system tip protein SipD in complex with deoxycholate and chenodeoxycholate
The crystal structures of the Salmonella type III secretion system tip protein SipD in complex with deoxycholate and chenodeoxycholate
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DOI：
10.1002/pro.537
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发表时间：
2011-01-01
期刊：
影响因子：
8
通讯作者：
De Guzman, Roberto N.
中科院分区：
文献类型：
--
作者：
Chatterjee, Srirupa;Zhong, Dalian;De Guzman, Roberto N.
III型分泌系统（T3 SS）是许多人类致病菌（包括沙门氏菌和志贺氏菌）毒力所需的蛋白质注射纳米机器人。T3 SS的一个重要组成部分是tip蛋白，沙门氏菌SipD和志贺氏菌iPad tip蛋白与胆汁盐相互作用，胆汁盐充当这些肠道病原体的环境传感器。SipD和iPad具有长的中央卷曲螺旋，并且它们的N-末端区域形成α-螺旋发夹和短螺旋α 3，其挤压卷曲螺旋。使用AutoDock，其他人预测胆盐脱氧胆酸盐在由α-螺旋发夹及其长的中央卷曲螺旋形成的裂缝中结合iPad。然而，NMR化学位移映射表明，受胆汁盐影响最大的SipD残基位于螺旋α 3附近的无序区域。因此，胆汁盐如何与SipD和iPad相互作用尚不清楚。在这里，我们报告的晶体结构的SipD的复合物与胆汁盐脱氧胆酸盐和鹅脱氧胆酸盐。胆盐结合SipD的区域不同于iPad的预测区域。在SipD中，胆汁盐结合螺旋α 3的一部分和长的中央卷曲螺旋的C-末端，朝向蛋白质的C-末端。我们讨论了胆盐如何与SipD和iPad相互作用的差异的生物学意义。
The type III secretion system (T3SS) is a protein injection nanomachinery required for virulence by many human pathogenic bacteria including Salmonella and Shigella. An essential component of the T3SS is the tip protein and the Salmonella SipD and the Shigella IpaD tip proteins interact with bile salts, which serve as environmental sensors for these enteric pathogens. SipD and IpaD have long central coiled coils and their N-terminal regions form alpha-helical hairpins and a short helix alpha 3 that pack against the coiled coil. Using AutoDock, others have predicted that the bile salt deoxycholate binds IpaD in a cleft formed by the alpha-helical hairpin and its long central coiled coil. NMR chemical shift mapping, however, indicated that the SipD residues most affected by bile salts are located in a disordered region near helix alpha 3. Thus, how bile salts interact with SipD and IpaD is unclear. Here, we report the crystal structures of SipD in complex with the bile salts deoxycholate and chenodeoxycholate. Bile salts bind SipD in a region different from what was predicted for IpaD. In SipD, bile salts bind part of helix alpha 3 and the C-terminus of the long central coiled coil, towards the C-terminus of the protein. We discuss the biological implication of the differences in how bile salts interact with SipD and IpaD.