› 8yw5

Electron Microscopy
2.84Å resolution

Cryo-EM structure of the retatrutide-bound human GCGR-Gs complex

Released:
DOI: 10.2210/pdb8yw5/pdb
PDB entry 8yw5 coloured by chain, front view.
PDB entry 8yw5 coloured by chain, side view.
PDB entry 8yw5 coloured by chain, top view.
Source organisms:
Primary publication:
Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide.
Li W, Zhou Q, Cong Z, Yuan Q, Li W, Zhao F, Xu HE, Zhao LH, Yang D, Wang MW
Cell Discov 10 77 (2024)
PMID: 39019866
Related structures: EMD-39623

Function and Biology Details

Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
hetero hexamer (preferred)
PDBe Complex ID:
PDB-CPX-248764 (preferred)
Entry contents:
6 distinct polypeptide molecules
Macromolecules (6 distinct):
Retatrutide Chain: P
Molecule details ›
Chain: P
Length: 30 amino acids
Theoretical weight: 3.36 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
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:
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%)
  • Best match: P63092-4 (Residues: 1-395)
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: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P62873 (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: 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: 140 amino acids
Theoretical weight: 15.34 KDa
Source organism: synthetic construct
Expression system: Escherichia coli

Ligands and Environments

No bound ligands
2 modified residues:
Ligand AIB 2 x AIB
Ligand 2ML 1 x 2ML

Experiments and Validation Details

Entry percentile scores
Resolution: 2.84Å
Relevant EMDB volumes: EMD-39623
Expression systems:
  • Spodoptera frugiperda
  • Escherichia coli

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