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科学家绘制出RGS蛋白调控G蛋白信号的全局图谱
作者:小柯机器人 发布时间:2020/10/4 22:53:53

近日,美国斯克里普斯研究所Kirill A. Martemyanov团队绘制出RGS蛋白调控G蛋白信号的全局图谱。相关论文于2020年10月1日在线发表于国际学术期刊《细胞》。

为了解G蛋白信号调节子(RGS)调节G蛋白α亚基(Gα)调控选择性的原理,研究人员使用活细胞中的实时动力学测量方法研究了所有经典人类RGS蛋白的催化活性及其对整套Gα底物的选择性。数据揭示了控制RGS-Gα识别的规则、其选择性的结构基础,并提供了选择性工程化RGS蛋白的原理。
 
该研究还通过祖先重建探索了RGS-Gα选择性的进化,并证明了RGS中天然存在的非同义变体如何改变信号传导。这些结果为解码信号选择性提供了一个蓝图,并增进了人们对分子识别原理的理解。
 
据悉,通过使Gα失活的RGS蛋白可以控制G蛋白信号的程度和时间。哺乳动物基因组编码20个经典的RGS和16个Gα基因,在生理和疾病中起关键作用。
 
附:英文原文

Title: A Global Map of G Protein Signaling Regulation by RGS Proteins

Author: Ikuo Masuho, Santhanam Balaji, Brian S. Muntean, Nickolas K. Skamangas, Sreenivas Chavali, John J.G. Tesmer, M. Madan Babu, Kirill A. Martemyanov

Issue&Volume: 2020-10-1

Abstract: The control over the extent and timing of G protein signaling is provided by the regulatorof G protein signaling (RGS) proteins that deactivate G protein α subunits (Gα). Mammaliangenomes encode 20 canonical RGS and 16 Gα genes with key roles in physiology and disease.To understand the principles governing the selectivity of Gα regulation by RGS, weexamine the catalytic activity of all canonical human RGS proteins and their selectivityfor a complete set of Gα substrates using real-time kinetic measurements in livingcells. The data reveal rules governing RGS-Gα recognition, the structural basis ofits selectivity, and provide principles for engineering RGS proteins with definedselectivity. The study also explores the evolution of RGS-Gα selectivity through ancestralreconstruction and demonstrates how naturally occurring non-synonymous variants inRGS alter signaling. These results provide a blueprint for decoding signaling selectivityand advance our understanding of molecular recognition principles.

DOI: 10.1016/j.cell.2020.08.052

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31140-5

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/