7TMW

Cryo-EM structure of the relaxin receptor RXFP1 in complex with heterotrimeric Gs

7TMW の概要

• エントリーDOI: 10.2210/pdb7tmw/pdb
• EMDBエントリー: 26003
• 分子名称: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (4 entities in total)
• 機能のキーワード: gpcr, complex, signaling, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177282.42

構造登録者

Erlandson, S.C.,Rawson, S.,Kruse, A.C. (登録日: 2022-01-20, 公開日: 2023-02-15, 最終更新日: 2023-08-09)

主引用文献

Erlandson, S.C.,Rawson, S.,Osei-Owusu, J.,Brock, K.P.,Liu, X.,Paulo, J.A.,Mintseris, J.,Gygi, S.P.,Marks, D.S.,Cong, X.,Kruse, A.C.
The relaxin receptor RXFP1 signals through a mechanism of autoinhibition.
Nat.Chem.Biol., 19:1013-1021, 2023

PubMed Abstract: The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor (GPCR) with an ectodomain consisting of a low-density lipoprotein receptor class A (LDLa) module and leucine-rich repeats. The mechanism of RXFP1 signal transduction is clearly distinct from that of other GPCRs, but remains very poorly understood. In the present study, we determine the cryo-electron microscopy structure of active-state human RXFP1, bound to a single-chain version of the endogenous agonist relaxin-2 and the heterotrimeric G protein. Evolutionary coupling analysis and structure-guided functional experiments reveal that RXFP1 signals through a mechanism of autoinhibition. Our results explain how an unusual GPCR family functions, providing a path to rational drug development targeting the relaxin receptors.

PubMed: 37081311
DOI: 10.1038/s41589-023-01321-6

実験手法

ELECTRON MICROSCOPY (3.2 Å)