Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain
Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain
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DOI：
10.1073/pnas.95.4.1381
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发表时间：
1998-02-17
影响因子：
11.1
通讯作者：
West, AH
中科院分区：
文献类型：
--
作者：
Djordjevic, S;Goudreau, PN;West, AH
我们报告的X-射线晶体结构的甲基酯酶切布，磷酸化激活的反应调节剂参与可逆修改的细菌趋化性受体。甲基酯酶切布和甲基转移酶CheR通过控制受体甲基化水平来调节趋化性受体的信号输出。切布的结构，其中包括一个N-末端的调节结构域和一个C-末端的催化结构域连接的接头，解决了分子置换方法使用独立的搜索模型的两个结构域。在未磷酸化的切布中，N-末端结构域与C-末端结构域的活性位点结合，从而通过直接限制进入活性位点来抑制甲基酯酶活性。我们建议，磷酸化的切布诱导的构象变化的监管结构域，破坏域接口，导致重新定位的域，并允许访问的活性位点。两种伴随受体修饰酶切布和切R之间的结构相似性表明了进化和/或功能关系。具体而言，磷酸化的N-末端结构域的切布可能有助于与受体的相互作用，类似于假定的作用的N-末端结构域的切R。检查表面的N-末端调控结构域的切布表明，尽管一个共同的折叠整个反应调节家族，用于蛋白质-蛋白质相互作用的表面显着不同。切布和其他反应调节剂之间的比较表明，类似的表面用于不同的功能，相反，类似的功能是由不同的分子表面介导的。
We report the x-ray crystal structure of the methylesterase CheB, a phosphorylation-activated response regulator involved in reversible modification of bacterial chemotaxis receptors. Methylesterase CheB and methyltransferase CheR modulate signaling output of the chemotaxis receptors by controlling the level of receptor methylation. The structure of CheB, which consists of an N-terminal regulatory domain and a C-terminal catalytic domain joined by a linker, was solved by molecular replacement methods using independent search models for the two domains. In unphosphorylated CheB, the N-terminal domain packs against the active site of the C-terminal domain and thus inhibits methylesterase activity by directly restricting access to the active site. We propose that phosphorylation of CheB induces a conformational change in the regulatory domain that disrupts the domain interface, resulting in a repositioning of the domains and allowing access to the active site. Structural similarity between the two companion receptor modification enzymes, CheB and CheR, suggests an evolutionary and/or functional relationship. Specifically, the phosphorylated N-terminal domain of CheB may facilitate interaction with the receptors, similar to the postulated role of the N-terminal domain of CheR. Examination of surfaces in the N-terminal regulatory domain of CheB suggests that despite a common fold throughout the response regulator family, surfaces used for protein-protein interactions differ significantly. Comparison between CheB and other response regulators indicates that analogous surfaces are used for different functions and conversely, similar functions are mediated by different molecular surfaces.