› 7v35

Electron Microscopy
3.4Å resolution

Cryo-EM structure of the GIPR/GLP-1R/GCGR triagonist peptide 20-bound human GCGR-Gs complex

Released:
DOI: 10.2210/pdb7v35/pdb
PDB entry 7v35 coloured by chain, front view.
PDB entry 7v35 coloured by chain, side view.
PDB entry 7v35 coloured by chain, top view.
Source organisms:
Primary publication:
Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors.
Zhao F, Zhou Q, Cong Z, Hang K, Zou X, Zhang C, Chen Y, Dai A, Liang A, Ming Q, Wang M, Chen LN, Xu P, Chang R, Feng W, Xia T, Zhang Y, Wu B, Yang D, Zhao L, Xu HE, Wang MW
Nat Commun 13 1057 (2022)
PMID: 35217653
Related structures: EMD-31676

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero hexamer (preferred)
PDBe Complex ID:
PDB-CPX-211257 (preferred)
Entry contents:
6 distinct polypeptide molecules
Macromolecules (6 distinct):
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short Chain: A
Molecule details ›
Chain: A
Length: 394 amino acids
Theoretical weight: 45.68 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63092 (Residues: 1-394; Coverage: 100%)
Gene names: GNAS, GNAS1, GSP
Sequence domains: G-protein alpha subunit
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 Chain: B
Molecule details ›
Chain: B
Length: 345 amino acids
Theoretical weight: 37.92 KDa
Source organism: Rattus norvegicus
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P54311 (Residues: 2-340; Coverage: 100%)
Gene name: Gnb1
Sequence domains: WD domain, G-beta repeat
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 Chain: C
Molecule details ›
Chain: C
Length: 71 amino acids
Theoretical weight: 7.86 KDa
Source organism: Bos taurus
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63212 (Residues: 1-71; Coverage: 100%)
Gene name: GNG2
Sequence domains: GGL domain
Nanobody-35 Chain: N
Molecule details ›
Chain: N
Length: 140 amino acids
Theoretical weight: 15.34 KDa
Source organism: synthetic construct
Expression system: Escherichia coli
Peptide 20 Chain: P
Molecule details ›
Chain: P
Length: 39 amino acids
Theoretical weight: 4.18 KDa
Source organism: synthetic construct
Expression system: Not provided
Glucagon receptor Chain: R
Molecule details ›
Chain: R
Length: 406 amino acids
Theoretical weight: 46.74 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P47871 (Residues: 27-432; Coverage: 90%)
Gene name: GCGR
Sequence domains:

Ligands and Environments

1 bound ligand:
Ligand D6M 1 x D6M
1 modified residue:
Ligand AIB 1 x AIB

Experiments and Validation Details

Entry percentile scores
Resolution: 3.4Å
Relevant EMDB volumes: EMD-31676
Expression systems:
  • Spodoptera frugiperda
  • Escherichia coli
  • Not provided

Quick links

Citations

11 review citations

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review.
Chavda et al. (2022)
10 more

2 mentions without citation

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.
Wong et al. (2023)
1 more