上海科技大学刘志杰、华甜等研究人员合作解析了CXC趋化因子受体2激活和信号传导的结构基础。相关论文于2020年7月1日在线发表在《自然》杂志上。
Title: Structural basis of CXC chemokine receptor 2 activation and signalling
Author: Kaiwen Liu, Lijie Wu, Shuguang Yuan, Meng Wu, Yueming Xu, Qianqian Sun, Shu Li, Suwen Zhao, Tian Hua, Zhi-Jie Liu
Issue&Volume: 2020-07-01
Abstract: Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions, such as inflammation and cancer1. Although ample efforts have been invested into the structural investigation of the chemokine receptors and receptor–chemokine recognition2–4, less is known about endogenous chemokine-induced receptor activation and G protein coupling. Here, we report the cryo-electron microscopy structures of interleukin-8 (IL8, also known as CXCL8)-activated human CXC chemokine receptor 2 (CXCR2) in complex with Gi protein, along with a designed allosteric antagonist-bound CXCR2 crystal structure. Our results uncover a unique shallow binding mode between CXCL8 and CXCR2, as well as CXCR2–Gi protein interactions. Further structural analysis of CXCR2’s inactive and active states reveals a distinct activation process and the competitive small molecule antagonism of chemokine receptors. In addition, this study provides new insights into how a G protein-coupled receptor (GPCR) is activated by an endogenous protein molecule, which will assist the rational development of therapeutics targeting the chemokine system for better pharmacological profiles.
DOI: 10.1038/s41586-020-2492-5
Source: https://www.nature.com/articles/s41586-020-2492-5
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
本期文章:《自然》:Online/在线发表