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G蛋白偶联受体介导Gαi和βarrestin的非典型结合
作者:小柯机器人 发布时间:2021/1/22 16:51:13

美国杜克大学Sudarshan Rajagopal小组的最新研究揭示了由异三聚体鸟嘌呤核苷酸结合蛋白(G蛋白)偶联受体(GPCR)介导的Gαi和β-arrestin非典型支架。相关论文于2021年1月21日发表在《科学》杂志上。

研究人员发现GPCRs促进Gαi蛋白亚家族成员和β-arrestins之间的直接相互作用,无论其经典Gαi蛋白亚型偶联如何。Gαi:β-arrestin复合物结合细胞外信号调节激酶(ERK),破坏该复合物会导致ERK失活和细胞迁移,这与在某些信号传到过程中β-arrestin需要与Gαi发生功能性相互作用相一致。

该结果揭示了不同于经典G蛋白激活的GPCR信号传导机制,其中GPCR会诱导Gαi:β-arrestin信号复合物的形成。

据介绍,GPCR是常见的药物靶点,并与特定的Gα蛋白亚型和β-arrestin衔接子蛋白结合。G蛋白和β-arrestin介导的信号传导被认为是可分离的。

附:英文原文

Title: Noncanonical scaffolding of Gαi and β-arrestin by G protein–coupled receptors

Author: Jeffrey S. Smith, Thomas F. Pack, Asuka Inoue, Claudia Lee, Kevin Zheng, Issac Choi, Dylan S. Eiger, Anmol Warman, Xinyu Xiong, Zhiyuan Ma, Gayathri Viswanathan, Ian M. Levitan, Lauren K. Rochelle, Dean P. Staus, Joshua C. Snyder, Alem W. Kahsai, Marc G. Caron, Sudarshan Rajagopal

Issue&Volume: 2021/02/21

Abstract: Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific Gα protein subtypes and β-arrestin adaptor proteins. G protein- and β-arrestin-mediated signaling have been considered separable. We show GPCRs promote a direct interaction between Gαi protein subtype family members and β-arrestins, regardless of their canonical Gαi protein subtype coupling. Gαi:β-arrestin complexes bound extracellular signal-regulated kinase (ERK) and their disruption impaired both ERK activation and cell migration, consistent with β-arrestins requiring a functional interaction with Gαi for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of Gαi:β-arrestin signaling complexes.

DOI: 10.1126/science.aay1833

Source: https://science.sciencemag.org/content/early/2021/01/21/science.aay1833

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037