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TitleStructural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.
Journal, issue, pagesCommun Biol, Vol. 5, Issue 1, Page 707, Year 2022
Publish dateJul 15, 2022
AuthorsShota Suzuki / Momoko Iida / Yoko Hiroaki / Kotaro Tanaka / Akihiro Kawamoto / Takayuki Kato / Atsunori Oshima /
PubMed AbstractMrgD, 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.
External linksCommun Biol / PubMed:35840655 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.2 Å
Structure data

33554

7y12

EMDB-33554, PDB-7y12:
Cryo-EM structure of MrgD-Gi complex with beta-alanine
Method: EM (single particle) / Resolution: 3.1 Å

33555

7y13

EMDB-33555, PDB-7y13:
Cryo-EM structure of apo-state MrgD-Gi complex (local)
Method: EM (single particle) / Resolution: 3.1 Å

33556

7y14

EMDB-33556, PDB-7y14:
Cryo-EM structure of MrgD-Gi complex with beta-alanine (local)
Method: EM (single particle) / Resolution: 3.2 Å

33557

7y15

EMDB-33557, PDB-7y15:
Cryo-EM structure of apo-state MrgD-Gi complex
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-BAL:
BETA-ALANINE

ChemComp-PLM:
PALMITIC ACID

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • synthetic construct (others)
  • escherichia coli (E. coli)
KeywordsSIGNALING PROTEIN / GPCR / Complex

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