+検索条件
-Structure paper
タイトル | Conformational transitions and activation of the adhesion receptor CD97. |
---|---|
ジャーナル・号・ページ | Mol Cell, Vol. 84, Issue 3, Page 570-583.e7, Year 2024 |
掲載日 | 2024年2月1日 |
著者 | Chunyou Mao / Ru-Jia Zhao / Ying-Jun Dong / Mingxin Gao / Li-Nan Chen / Chao Zhang / Peng Xiao / Jia Guo / Jiao Qin / Dan-Dan Shen / Su-Yu Ji / Shao-Kun Zang / Huibing Zhang / Wei-Wei Wang / Qingya Shen / Jin-Peng Sun / Yan Zhang / |
PubMed 要旨 | Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly ...Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts. |
リンク | Mol Cell / PubMed:38215752 |
手法 | EM (単粒子) |
解像度 | 2.33 - 4.32 Å |
構造データ | EMDB-35514, PDB-8ikj: EMDB-35516, PDB-8ikl: EMDB-38938: Cryo-EM structure of the inactive CD97 EMDB-38939: Cryo-EM structure of the inactive CD97 EMDB-38980: Cryo-EM structure of the inactive CD97 |
化合物 | ChemComp-NAG: |
由来 |
|
キーワード | MEMBRANE PROTEIN / adhension GPCR / CD97 / inactive / G13 / complex |