Leung Adelaine K W, Lucile White E, Ross Larry J, Reynolds Robert C, DeVito Joseph A, Borhani David W
Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, USA.
J Mol Biol. 2004 Sep 17;342(3):953-70. doi: 10.1016/j.jmb.2004.07.061.
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 2.08A 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.
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，分别为柠檬酸、GDP和GTPγS复合物，分辨率分别为1.89、2.60和2.08埃。结核分枝杆菌FtsZ结晶为紧密的侧向二聚体，与αβ-微管蛋白观察到的纵向聚合物不同。大肠杆菌FtsZ的突变数据表明，这种二聚体界面对于原丝和“Z环”的正确组装和功能很重要。二聚体界面处的α到β二级结构构象转换在空间上类似于G蛋白激活时表现出的开关I构象变化，并且具有许多特征。FtsZ活性位点中γ-磷酸的存在调节了“微管蛋白”环T3的构象（在空间上类似于G蛋白开关II）；γ-磷酸连接时T3的转换通过空间重叠直接与α到β转换偶联。此处首次在FtsZ中观察到的双重构象转换将GTP结合和水解与FtsZ（和微管蛋白）侧向组装和Z环收缩联系起来，这表明FtsZ、微管蛋白和G蛋白之间存在未被充分认识的功能类比。
