7YJ4

Cryo-EM structure of the INSL5-bound human relaxin family peptidereceptor 4 (RXFP4)-Gi complex

7YJ4 の概要

• エントリーDOI: 10.2210/pdb7yj4/pdb
• EMDBエントリー: 33871
• 分子名称: Insulin-like peptide INSL5 A chain, Insulin-like peptide INSL5 B chain, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (7 entities in total)
• 機能のキーワード: human relaxin family peptide receptor 4, g protein-coupled receptor, ligand recognition, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 158937.16

構造登録者

Chen, Y.,Zhou, Q.T.,Wang, J.,Xu, Y.W.,Wang, Y.,Yan, J.H.,Wang, Y.B.,Zhu, Q.,Zhao, F.H.,Li, C.H.,Chen, C.W.,Cai, X.Q.,Bathgate, R.A.D.,Shen, C.,Liu, H.,Xu, H.E.,Yang, D.H.,Wang, M.W. (登録日: 2022-07-19, 公開日: 2023-03-01, 最終更新日: 2024-10-23)

主引用文献

Chen, Y.,Zhou, Q.,Wang, J.,Xu, Y.,Wang, Y.,Yan, J.,Wang, Y.,Zhu, Q.,Zhao, F.,Li, C.,Chen, C.W.,Cai, X.,Bathgate, R.A.D.,Shen, C.,Eric Xu, H.,Yang, D.,Liu, H.,Wang, M.W.
Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4).
Nat Commun, 14:492-492, 2023

PubMed Abstract: 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.

PubMed: 36717591
DOI: 10.1038/s41467-023-36182-z

実験手法

ELECTRON MICROSCOPY (3.19 Å)