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-Structure paper
タイトル | Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM. |
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ジャーナル・号・ページ | Commun Biol, Vol. 5, Issue 1, Page 707, Year 2022 |
掲載日 | 2022年7月15日 |
著者 | Shota Suzuki / Momoko Iida / Yoko Hiroaki / Kotaro Tanaka / Akihiro Kawamoto / Takayuki Kato / Atsunori Oshima / |
PubMed 要旨 | MrgD, 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 β-alanine, and is involved in pain ...MrgD, 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 β-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 β-alanine-bound and apo states at 3.1 Å and 2.8 Å resolution, respectively. These structures show that β-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. |
リンク | Commun Biol / PubMed:35840655 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.2 Å |
構造データ | EMDB-33554, PDB-7y12: EMDB-33555, PDB-7y13: EMDB-33556, PDB-7y14: EMDB-33557, PDB-7y15: |
化合物 | ChemComp-BAL: ChemComp-PLM: ChemComp-HOH: |
由来 |
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キーワード | SIGNALING PROTEIN / GPCR / Complex |