7Y15

Cryo-EM structure of apo-state MrgD-Gi complex

Summary for 7Y15

• Entry DOI: 10.2210/pdb7y15/pdb
• EMDB information: 33557
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, 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)
• Functional Keywords: gpcr, complex, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 170418.25

Authors

Suzuki, S.,Iida, M.,Kawamoto, A.,Oshima, A. (deposition date: 2022-06-06, release date: 2022-07-20, Last modification date: 2024-11-06)

Primary citation

Suzuki, S.,Iida, M.,Hiroaki, Y.,Tanaka, K.,Kawamoto, A.,Kato, T.,Oshima, A.
Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.
Commun Biol, 5:707-707, 2022

PubMed Abstract: 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.

PubMed: 35840655
DOI: 10.1038/s42003-022-03668-3

Experimental method

ELECTRON MICROSCOPY (2.9 Å)