Disruption of chemoreceptor signalling arrays by high levels of CheW, the receptor-kinase coupling protein.
Disruption of chemoreceptor signalling arrays by high levels of CheW, the receptor-kinase coupling protein.
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DOI：
10.1111/j.1365-2958.2009.07032.x
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发表时间：
2010-03
影响因子：
3.6
通讯作者：
Studdert CA
中科院分区：
文献类型：
--
作者：
Cardozo MJ;Massazza DA;Parkinson JS;Studdert CA
在大肠杆菌的趋化信号传导过程中，小细胞质 CheW 蛋白将组氨酸激酶 CheA 与化学感受器控制偶联。尽管 CheW 对于受体信号复合物的组装和操作至关重要，但化学计量过量的 CheW 会破坏趋化行为。为了探索 CheW 过量效应的机制，我们测量了高细胞水平的野生型 CheW 和几种与受体分子结合亲和力降低或增强的 CheW 变体的生理后果。我们发现高水平的 CheW 会干扰三聚体组装，阻止 CheA 激活，阻止簇形成，破坏趋化能力，并升高受体甲基化水平。这些影响的严重程度与 CheW 变体的受体结合亲和力相似。由于三聚体形成可能是三元信号复合物和高阶受体阵列组装中的必然步骤，因此我们认为所有 CheW 过量效应均源于三聚体组装的破坏。我们提出受体二聚体中的 CheW 结合位点与其三聚体接触位点重叠，并且高水平的 CheW 使受体结合位点饱和，从而阻止三聚体组装。 CheW 捕获的受体二聚体似乎是甲基转移酶反应的改良底物，但不能激活 CheA 或组装成簇，而这些过程对于趋化信号传导至关重要。
During chemotactic signaling by Escherichia coli, the small cytoplasmic CheW protein couples the histidine kinase CheA to chemoreceptor control. Although essential for assembly and operation of receptor signaling complexes, CheW in stoichiometric excess disrupts chemotactic behavior. To explore the mechanism of the CheW excess effect, we measured the physiological consequences of high cellular levels of wild-type CheW and of several CheW variants with reduced or enhanced binding affinities for receptor molecules. We found that high levels of CheW interfered with trimer assembly, prevented CheA activation, blocked cluster formation, disrupted chemotactic ability, and elevated receptor methylation levels. The severity of these effects paralleled the receptor binding affinities of the CheW variants. Because trimer formation may be an obligate step in the assembly of ternary signaling complexes and higher-order receptor arrays, we suggest that all CheW excess effects stem from disruption of trimer assembly. We propose that the CheW-binding sites in receptor dimers overlap their trimer contact sites and that high levels of CheW saturate the receptor binding sites, preventing trimer assembly. The CheW-trapped receptor dimers seem to be improved substrates for methyltransferase reactions, but cannot activate CheA or assemble into clusters, processes that are essential for chemotactic signaling.
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影响因子：
3.6
作者：
Briegel, Ariane;Ding, H. Jane;Jensen, Grant J.
通讯作者：
Jensen, Grant J.
DOI：
10.1073/pnas.0802868105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Besschetnova, Tatiana Y.;Montefusco, David J.;Weis, Robert M.
通讯作者：
Weis, Robert M.
新型克隆载体的构建和特性分析 2. 多用途克隆系统
影响因子：
3.5
作者：
BOLIVAR, F;RODRIGUEZ, RL;FALKOW, S
通讯作者：
FALKOW, S
影响因子：
3.2
作者：
AMES, P;PARKINSON, JS
通讯作者：
PARKINSON, JS
影响因子：
3.2
作者：
CHANG, ACY;COHEN, SN
通讯作者：
COHEN, SN