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-Structure paper
Title | Structure, function and pharmacology of human itch GPCRs. |
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Journal, issue, pages | Nature, Vol. 600, Issue 7887, Page 170-175, Year 2021 |
Publish date | Nov 17, 2021 |
Authors | Can Cao / Hye Jin Kang / Isha Singh / He Chen / Chengwei Zhang / Wenlei Ye / Byron W Hayes / Jing Liu / Ryan H Gumpper / Brian J Bender / Samuel T Slocum / Brian E Krumm / Katherine Lansu / John D McCorvy / Wesley K Kroeze / Justin G English / Jeffrey F DiBerto / Reid H J Olsen / Xi-Ping Huang / Shicheng Zhang / Yongfeng Liu / Kuglae Kim / Joel Karpiak / Lily Y Jan / Soman N Abraham / Jian Jin / Brian K Shoichet / Jonathan F Fay / Bryan L Roth / |
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 ...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. |
External links | Nature / PubMed:34789874 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.45 - 2.9 Å |
Structure data | EMDB-24896, PDB-7s8l: EMDB-24897, PDB-7s8m: EMDB-24898, PDB-7s8n: EMDB-24899, PDB-7s8o: EMDB-24900, PDB-7s8p: |
Chemicals | ChemComp-8IU: ChemComp-8IX: |
Source |
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Keywords | SIGNALING PROTEIN / GPCR |