› 7rbt

Electron Microscopy
3.08Å resolution

cryo-EM structure of human Gastric inhibitory polypeptide receptor GIPR bound to tirzepatide

Released:
DOI: 10.2210/pdb7rbt/pdb
PDB entry 7rbt coloured by chain, front view.
PDB entry 7rbt coloured by chain, side view.
PDB entry 7rbt coloured by chain, top view.
Source organisms:
Primary publication:
Structural determinants of dual incretin receptor agonism by tirzepatide.
Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW
Proc Natl Acad Sci U S A 119 e2116506119 (2022)
PMID: 35333651
Related structures: EMD-24401

Function and Biology Details

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

Structure analysis Details

Assembly composition:
hetero heptamer (preferred)
PDBe Complex ID:
PDB-CPX-242876 (preferred)
Entry contents:
7 distinct polypeptide molecules
Macromolecules (7 distinct):
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short Chain: A
Molecule details ›
Chain: A
Length: 373 amino acids
Theoretical weight: 43.39 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P63092 (Residues: 26-394; Coverage: 90%)
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: 350 amino acids
Theoretical weight: 38.53 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P62873 (Residues: 2-340; Coverage: 100%)
Gene name: GNB1
Sequence domains: WD domain, G-beta repeat
Single-chain variable fragment 16 Chain: E
Molecule details ›
Chain: E
Length: 297 amino acids
Theoretical weight: 31.87 KDa
Source organism: Mus musculus
Expression system: Spodoptera frugiperda
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 Chain: G
Molecule details ›
Chain: G
Length: 71 amino acids
Theoretical weight: 7.86 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P59768 (Residues: 1-71; Coverage: 100%)
Gene name: GNG2
Sequence domains: GGL domain
nanobody 35 Chain: N
Molecule details ›
Chain: N
Length: 160 amino acids
Theoretical weight: 17.35 KDa
Source organism: Lama glama
Expression system: Escherichia coli
Tirzepatide Chain: P
Molecule details ›
Chain: P
Length: 39 amino acids
Theoretical weight: 4.07 KDa
Source organism: Homo sapiens
Expression system: Not provided
Gastric inhibitory polypeptide receptor Chain: R
Molecule details ›
Chain: R
Length: 463 amino acids
Theoretical weight: 52.87 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P48546 (Residues: 22-466; Coverage: 100%)
Gene name: GIPR
Sequence domains:

Ligands and Environments

1 bound ligand:
Ligand 41Y 1 x 41Y
1 modified residue:
Ligand AIB 2 x AIB

Experiments and Validation Details

Entry percentile scores
Resolution: 3.08Å
Relevant EMDB volumes: EMD-24401
Expression systems:
  • Trichoplusia ni
  • Spodoptera frugiperda
  • Escherichia coli
  • Not provided

Quick links

Citations

9 review citations

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction.
Nauck et al. (2022)
8 more

3 mentions without citation

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