Biology Department, University of Utah, Salt Lake City, UT 84112.
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106.
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7583-E7591. doi: 10.1073/pnas.1709075114. Epub 2017 Aug 21.
A sensory adaptation system that tunes chemoreceptor sensitivity enables motile cells to track chemical gradients with high sensitivity over a wide dynamic range. Sensory adaptation involves feedback control of covalent receptor modifications by two enzymes: CheR, a methyltransferase, and CheB, a methylesterase. This study describes a CheR function that opposes the signaling consequences of its catalytic activity. In the presence of CheR, a variety of mutant serine chemoreceptors displayed up to 40-fold enhanced detection sensitivity to chemoeffector stimuli. This response enhancement effect did not require the known catalytic activity of CheR, but did involve a binding interaction between CheR and receptor molecules. Response enhancement was maximal at low CheR:receptor stoichiometry and quantitative analyses argued against a reversible binding interaction that simply shifts the ON-OFF equilibrium of receptor signaling complexes. Rather, a short-lived CheR binding interaction appears to promote a long-lasting change in receptor molecules, either a covalent modification or conformation that enhances their response to attractant ligands.
一种感觉适应系统可以调节化学感受器的敏感性，使游动细胞能够在宽动态范围内以高灵敏度跟踪化学梯度。感觉适应涉及由两种酶对共价受体修饰的反馈控制：CheR，一种甲基转移酶，和 CheB，一种甲酯酶。本研究描述了 CheR 的一种功能，该功能与它的催化活性的信号转导后果相反。在 CheR 的存在下，各种突变丝氨酸化学感受器对化学引诱剂刺激的检测灵敏度提高了 40 倍。这种响应增强效应不需要 CheR 的已知催化活性，但确实涉及 CheR 和受体分子之间的结合相互作用。在 CheR:受体低计量比下，响应增强达到最大值，定量分析表明，这不是一种简单地改变受体信号转导复合物的 ON-OFF 平衡的可逆结合相互作用。相反，CheR 结合相互作用似乎会促进受体分子的持久变化，无论是增强它们对吸引配体的反应的共价修饰还是构象变化。
