› 7vab

Electron Microscopy
3.2Å resolution

Cryo-EM structure of the non-acylated tirzepatide (LY3298176)-bound human GIPR-Gs complex

Released:
DOI: 10.2210/pdb7vab/pdb
PDB entry 7vab coloured by chain, front view.
PDB entry 7vab coloured by chain, side view.
PDB entry 7vab 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-31836

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-211272 (preferred)
Entry contents:
6 distinct polypeptide molecules
Macromolecules (6 distinct):
Gastric inhibitory polypeptide receptor Chain: R
Molecule details ›
Chain: R
Length: 573 amino acids
Theoretical weight: 64.95 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P48546 (Residues: 22-421; Coverage: 90%)
Gene name: GIPR
Sequence domains:
Non-acylated_tirzepatide Chain: P
Molecule details ›
Chain: P
Length: 39 amino acids
Theoretical weight: 4.07 KDa
Source organism: synthetic construct
Expression system: Not provided
Guanine nucleotide-binding protein G(i) subunit alpha-1; Guanine nucleotide-binding protein G(s) subunit alpha isoforms short Chain: A
Molecule details ›
Chain: A
Length: 361 amino acids
Theoretical weight: 41.88 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63096 (Residues: 1-19, 61-181, 229-242; Coverage: 41%)
  • Canonical: P63092 (Residues: 27-67, 205-251, 266-394; Coverage: 55%)
Gene names: GNAI1, 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: 371 amino acids
Theoretical weight: 40.23 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: G
Molecule details ›
Chain: G
Length: 64 amino acids
Theoretical weight: 7.04 KDa
Source organism: Bos taurus
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63212 (Residues: 1-64; Coverage: 90%)
Gene name: GNG2
Sequence domains: GGL domain
Nonobody-35 Chain: N
Molecule details ›
Chain: N
Length: 140 amino acids
Theoretical weight: 15.34 KDa
Source organism: synthetic construct
Expression system: Escherichia coli

Ligands and Environments

1 bound ligand:
Ligand CLR 6 x CLR
1 modified residue:
Ligand AIB 2 x AIB

Experiments and Validation Details

Entry percentile scores
Resolution: 3.2Å
Relevant EMDB volumes: EMD-31836
Expression systems:
  • Spodoptera frugiperda
  • Not provided
  • Escherichia coli

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

3 mentions without citation

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