Structural highlights
Publication Abstract from PubMedMrgD, a member of the Mas-related G protein-coupled receptor (MRGPR) family, has high basal activity for Gi activation. It recognizes endogenous ligands, such as beta-alanine, and is involved in pain and itch signaling. The lack of a high-resolution structure for MrgD hinders our understanding of whether its activation is ligand-dependent or constitutive. Here, we report two cryo-EM structures of the MrgD-Gi complex in the beta-alanine-bound and apo states at 3.1 A and 2.8 A resolution, respectively. These structures show that beta-alanine is bound to a shallow pocket at the extracellular domains. The extracellular half of the sixth transmembrane helix undergoes a significant movement and is tightly packed into the third transmembrane helix through hydrophobic residues, creating the active form. Our structures demonstrate a structural basis for the characteristic ligand recognition of MrgD. These findings provide a framework to guide drug designs targeting the MrgD receptor. Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.,Suzuki S, Iida M, Hiroaki Y, Tanaka K, Kawamoto A, Kato T, Oshima A Commun Biol. 2022 Jul 15;5(1):707. doi: 10.1038/s42003-022-03668-3. PMID:35840655[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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