Hanson Susan M, Gurevich Eugenia V, Vishnivetskiy Sergey A, Ahmed Mohamed R, Song Xiufeng, Gurevich Vsevolod V
Department of Pharmacology, Vanderbilt University, 2200 Pierce Avenue, PRB, Room 418, Nashville, TN 37232, USA.
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3125-8. doi: 10.1073/pnas.0610886104. Epub 2007 Feb 20.
Arrestins (Arrs) are ubiquitous regulators of the most numerous family of signaling proteins, G protein-coupled receptors. Two models of the Arr-receptor interaction have been proposed: the binding of one Arr to an individual receptor or to two receptors in a dimer. To determine the binding stoichiometry in vivo, we used rod photoreceptors where rhodopsin (Rh) and Arr are expressed at comparably high levels and where Arr localization in the light is determined by its binding to activated Rh. Genetic manipulation of the expression of both proteins shows that the maximum amount of Arr that moves to the Rh-containing compartment exceeds 80%, but not 100%, of the molar amount of Rh present. In vitro experiments with purified proteins confirm that Arr "saturates" Rh at a 1:1 ratio. Thus, a single Rh molecule is necessary and sufficient to bind Arr. Remarkable structural conservation among receptors and Arrs strongly suggests that all Arr subtypes bind individual molecules of their cognate receptors.
抑制蛋白（Arrs）是信号蛋白中数量最多的家族——G蛋白偶联受体的普遍调节剂。关于抑制蛋白与受体相互作用，已提出两种模型：一种抑制蛋白与单个受体结合，或与二聚体中的两个受体结合。为了确定体内的结合化学计量，我们使用了视杆光感受器，其中视紫红质（Rh）和抑制蛋白以相当高的水平表达，并且抑制蛋白在光照下的定位由其与活化的视紫红质的结合决定。对这两种蛋白表达的基因操作表明，转移到含视紫红质区室的抑制蛋白的最大量超过了存在的视紫红质摩尔量的80%，但未达到100%。用纯化蛋白进行的体外实验证实，抑制蛋白以1:1的比例“饱和”视紫红质。因此，单个视紫红质分子结合抑制蛋白是必要且充分的。受体和抑制蛋白之间显著的结构保守性强烈表明，所有抑制蛋白亚型都与其同源受体的单个分子结合。
