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8JGF

CryoEM structure of Gq-coupled MRGPRX1 with peptide agonist BAM8-22

Summary for 8JGF
Entry DOI10.2210/pdb8jgf/pdb
EMDB information36232
DescriptorGuanine nucleotide-binding protein Gq, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Single-Chain Fragment Variable 16, ... (6 entities in total)
Functional Keywordsitch receptor, mas-related gpcrs, mgprx1, structural protein
Biological sourceHomo sapiens (human)
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Total number of polymer chains6
Total formula weight154904.64
Authors
Sun, J.P.,Xu, H.E.,Yang, F.,Liu, Z.M.,Guo, L.L.,Zhang, Y.M.,Fang, G.X.,Tie, L.,Zhuang, Y.M.,Xue, C.Y. (deposition date: 2023-05-20, release date: 2024-01-10)
Primary citationGuo, L.,Zhang, Y.,Fang, G.,Tie, L.,Zhuang, Y.,Xue, C.,Liu, Q.,Zhang, M.,Zhu, K.,You, C.,Xu, P.,Yuan, Q.,Zhang, C.,Liu, L.,Rong, N.,Peng, S.,Liu, Y.,Wang, C.,Luo, X.,Lv, Z.,Kang, D.,Yu, X.,Zhang, C.,Jiang, Y.,Dong, X.,Zhou, J.,Liu, Z.,Yang, F.,Eric Xu, H.,Sun, J.P.
Ligand recognition and G protein coupling of the human itch receptor MRGPRX1.
Nat Commun, 14:5004-5004, 2023
Cited by
PubMed Abstract: MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal "RF/RY" motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the GXPFGXF/W motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling.
PubMed: 37591889
DOI: 10.1038/s41467-023-40705-z
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.7 Å)
Structure validation

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