National Natural Science Foundation of China (NSFC)
81872915
中国
National Natural Science Foundation of China (NSFC)
82073904
中国
National Natural Science Foundation of China (NSFC)
82121005
中国
National Natural Science Foundation of China (NSFC)
81973373
中国
National Natural Science Foundation of China (NSFC)
82130105
中国
National Natural Science Foundation of China (NSFC)
21704064
中国
Other government
2021ZD0203400
Other government
2018YFA0507000
Other government
ZDKJ2021028
Other government
21JC1401600
Other government
1135837
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4). 著者: Yan Chen / Qingtong Zhou / Jiang Wang / Youwei Xu / Yun Wang / Jiahui Yan / Yibing Wang / Qi Zhu / Fenghui Zhao / Chenghao Li / Chuan-Wei Chen / Xiaoqing Cai / Ross A D Bathgate / Chun Shen / ...著者: Yan Chen / Qingtong Zhou / Jiang Wang / Youwei Xu / Yun Wang / Jiahui Yan / Yibing Wang / Qi Zhu / Fenghui Zhao / Chenghao Li / Chuan-Wei Chen / Xiaoqing Cai / Ross A D Bathgate / Chun Shen / H Eric Xu / Dehua Yang / Hong Liu / Ming-Wei Wang / 要旨: Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and ...Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and relaxin/insulin-like peptides. The latter bind to the human relaxin family peptide receptors (RXFPs). Here, we report three cryo-electron microscopy structures of RXFP4-G protein complexes in the presence of the endogenous ligand insulin-like peptide 5 (INSL5) or one of the two small molecule agonists, compound 4 and DC591053. The B chain of INSL5 adopts a single α-helix that penetrates into the orthosteric pocket, while the A chain sits above the orthosteric pocket, revealing a peptide-binding mode previously unknown. Together with mutagenesis and functional analyses, the key determinants responsible for the peptidomimetic agonism and subtype selectivity were identified. Our findings not only provide insights into ligand recognition and subtype selectivity among class A G protein-coupled receptors, but also expand the knowledge of signaling mechanisms in the insulin superfamily.
超分子 #1: Cryo-EM structure of the human relaxin family peptide receptor 4 ...
超分子
名称: Cryo-EM structure of the human relaxin family peptide receptor 4 in complex with compound 4 and G protein タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: #1-#5