澳大利亚莫纳什大学莫纳什药物科学研究所Patrick M. Sexton、Denise Wootten以及日本东京大学Radostin Danev课题组合作取得一项新突破。他们提出载脂蛋白和肽结合形式的G蛋白偶联受体（GPCR）的结构和动力学。该研究于2021年2月18日发表于《科学》杂志。

他们表达和纯化未修饰的载脂蛋白和与肽结合的降钙素基因相关肽（CGRP）受体，以确定它们的冷冻电镜结构，并使用氢-氘交换质谱（HDX-MS）和3D方差分析蛋白质构象动力学来补充这些结构冷冻电镜数据分析。连同他们先前发布的与Gs结合的活性CGRP受体复合物的结构，他们的工作为B1类GPCR激活机制提供了重要见解。

据了解，GPCR是细胞和器官之间信息传递的关键调节器。尽管如此，人们对apo状态下GPCR的行为以及激动剂结合后导致G蛋白募集和激活的构象变化的了解仍然有限。

附：英文原文

Title: Structure and dynamics of the CGRP receptor in apo and peptide-bound forms

Author: Tracy M. Josephs, Matthew J. Belousoff, Yi-Lynn Liang, Sarah J. Piper, Jianjun Cao, Daniel J. Garama, Katie Leach, Karen J. Gregory, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton

Issue&Volume: 2021/02/18

Abstract: G protein-coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only limited understanding of the behavior of GPCRs in the apo state and the conformational changes upon agonist binding that lead to G protein recruitment and activation. We expressed and purified unmodified apo and peptide-bound calcitonin gene-related peptide (CGRP) receptors to determine their cryo-EM structures and complemented these with analysis of protein conformational dynamics using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and 3D variance analysis of the cryo-EM data. Together with our previously published structure of the active, Gs-bound, CGRP receptor complex, our work provides important insight into mechanisms of class B1 GPCR activation.

DOI: 10.1126/science.abf7258

Source: https://science.sciencemag.org/content/early/2021/02/17/science.abf7258