Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches
Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches
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DOI：
10.1016/j.jmb.2004.07.061
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发表时间：
2004-09-17
影响因子：
5.6
通讯作者：
Borhani, DW
中科院分区：
文献类型：
--
作者：
Leung, AKW;White, EL;Borhani, DW
我们报道了结核分枝杆菌细胞分裂蛋白FtsZ的三种晶体结构，分别是柠檬酸盐、GDP和GTPGammaS复合体，分辨率分别为1.89、2.60和2.08埃。MtbFtsZ结晶为紧密的、横向取向的二聚体，不同于观察到的α-β-微管蛋白的纵向聚合物。在大肠杆菌FtsZ上的突变数据表明，这个二聚体界面对于正确的原丝和“Z-环”的组装和功能是重要的。位于二聚体界面的从α到β的二级结构构象开关在空间上类似于G蛋白激活时表现出的开关I构象变化，并具有许多特征。FtsZ活性部位中伽马-磷酸的存在调节“微管”环T3的构象(空间上类似于G蛋白开关II)；伽马-磷酸连接时的T3开关通过空间重叠直接耦合到α-β开关。首次在FtsZ中观察到的双构象开关将GTP与FtsZ(和微管蛋白)侧向组装和Z-环收缩联系在一起，它们暗示了FtsZ、微管蛋白和G-蛋白之间被低估的功能类似。(C)2004爱思唯尔有限公司。保留所有权利。
We report three crystal structures of the Mycobacterium tuberculosis cell division protein FtsZ, as the citrate, GDP, and GTPgammaS complexes, determined at 1.89, 2.60, and 2.08 Angstrom resolution. MtbFtsZ crystallized as a tight, laterally oriented dimer distinct from the longitudinal polymer observed for alphabeta-tubulin. Mutational data on Escherichia coli FtsZ suggest that this dimer interface is important for proper protofilament and "Z-ring" assembly and function. An alpha-to-beta secondary structure conformational switch at the dimer interface is spatially analogous to, and has many of the hallmarks of, the Switch I conformational changes exhibited by G-proteins upon activation. The presence of a gamma-phosphate in the FtsZ active site modulates the conformation of the "tubulin" loop T3 (spatially analogous to the G-protein Switch II); T3 switching upon gamma-phosphate ligation is directly coupled to the alpha-to-beta switch by steric overlap. The dual conformational switches observed here for the first time in an FtsZ link GTP binding and hydrolysis to FtsZ (and tubulin) lateral assembly and Z-ring contraction, and they are suggestive of an underappreciated functional analogy between FtsZ, tubulin and G-proteins. (C) 2004 Elsevier Ltd. All rights reserved.