7S8P

CryoEM structure of Gq-coupled MRGPRX4 with small molecule agonist MS47134

7S8P の概要

• エントリーDOI: 10.2210/pdb7s8p/pdb
• EMDBエントリー: 24900
• 分子名称: Gs-mini-Gq chimera, 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, ... (6 entities in total)
• 機能のキーワード: gpcr, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 157810.55

構造登録者

Cao, C.,Fay, J.F.,Gumpper, R.H.,Roth, B.L. (登録日: 2021-09-18, 公開日: 2021-11-17, 最終更新日: 2025-06-04)

主引用文献

Cao, C.,Kang, H.J.,Singh, I.,Chen, H.,Zhang, C.,Ye, W.,Hayes, B.W.,Liu, J.,Gumpper, R.H.,Bender, B.J.,Slocum, S.T.,Krumm, B.E.,Lansu, K.,McCorvy, J.D.,Kroeze, W.K.,English, J.G.,DiBerto, J.F.,Olsen, R.H.J.,Huang, X.P.,Zhang, S.,Liu, Y.,Kim, K.,Karpiak, J.,Jan, L.Y.,Abraham, S.N.,Jin, J.,Shoichet, B.K.,Fay, J.F.,Roth, B.L.
Structure, function and pharmacology of human itch GPCRs.
Nature, 600:170-175, 2021

PubMed Abstract: The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions. MRGPRX2 couples to both G and G in mast cells. Here we describe agonist-stabilized structures of MRGPRX2 coupled to G and G in ternary complexes with the endogenous peptide cortistatin-14 and with a synthetic agonist probe, respectively, and the development of potent antagonist probes for MRGPRX2. We also describe a specific MRGPRX4 agonist and the structure of this agonist in a complex with MRGPRX4 and G. Together, these findings should accelerate the structure-guided discovery of therapeutic agents for pain, itch and mast cell-mediated hypersensitivity.

PubMed: 34789874
DOI: 10.1038/s41586-021-04126-6

実験手法

ELECTRON MICROSCOPY (2.6 Å)