Receptor methylation controls the magnitude of stimulus-response coupling in bacterial chemotaxis
Receptor methylation controls the magnitude of stimulus-response coupling in bacterial chemotaxis
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DOI：
10.1074/jbc.m204325200
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发表时间：
2002-09-27
影响因子：
4.8
通讯作者：
Stock, JB
中科院分区：
文献类型：
--
作者：
Levit, MN;Stock, JB
能动的原核生物利用化学感受器-激酶阵列来感知介质的变化，并适当地调整它们的游泳行为。这个阵列由一个I型膜受体家族、一个组氨酸蛋白激酶(CHEA)和一个类似于Src的蛋白(CHEW)组成。引诱剂与化学受体的结合抑制了CHEA，这导致趋化反应调节因子(CHEY)的磷酸化减少。该系统对刺激的敏感性是由蛋白质甲基转移酶(CHER)和蛋白质甲酯酶(CHEB)调节的，这两个酶催化受体胞质区域中特定谷氨酰残基的甲基化和去甲基化。关于细菌趋化机制最基本的问题之一是配体与受体结合和CHEA抑制之间的定量关系。我们表明，受体谷氨酰修饰通过改变吸引剂结合和激酶抑制之间的增益(幅度放大)而导致适应，而不显著影响配体结合亲和力。该机制在引诱剂浓度的几个数量级上调节受体对背景刺激强度的敏感性。配体结合的协同效应似乎很小，其抑制激酶的Hill系数小于2，与谷氨酰修饰的状态无关。
Motile prokaryotes employ a chemoreceptor-kinase array to sense changes in the media and properly adjust their swimming behavior. This array is composed of a family of Type I membrane receptors, a histidine protein kinase (CheA), and an Src homology 3-like protein (CheW). Binding of an attractant to the chemoreceptors inhibits CheA, which results in decreased phosphorylation of the chemotaxis response regulator (CheY). Sensitivity of the system to stimuli is modulated by a protein methyltransferase (CheR) and a protein methylesterase (CheB) that catalyze the methylation and demethylation of specific glutamyl residues in the cytoplasmic domain of the receptors. One of the most fundamental unanswered questions concerning the bacterial chemotaxis mechanism is the quantitative relationship between ligand binding to receptors and CheA inhibition. We show that the receptor glutamyl modifications cause adaptation by changing the gain (magnitude amplification) between attractant binding and kinase inhibition without substantially affecting ligand binding affinity. The mechanism adjusts receptor sensitivity to background stimulus intensity over several orders of magnitude of attractant concentrations. The cooperative effects of ligand binding appear to be minimal with Hill coefficients for kinase inhibition less than 2, independent of the state of glutamyl modification.