8jir

Electron Microscopy
2.57Å resolution

Cryo-EM structure of the GLP-1R/GCGR dual agonist SAR425899-bound human GLP-1R-Gs complex

Released:
Primary publication:
Structural analysis of the dual agonism at GLP-1R and GCGR.
OpenAccess logo Proc Natl Acad Sci U S A 120 e2303696120 (2023)
PMID: 37549266
Related structures: EMD-36325

Function and Biology Details

Biochemical function:
Cellular component:

Structure analysis Details

Assembly composition:
hetero hexamer (preferred)
PDBe Complex ID:
PDB-CPX-545351 (preferred)
Entry contents:
6 distinct polypeptide molecules
Macromolecules (6 distinct):
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: 41.89 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63092 (Residues: 1-3, 27-67, 205-251, 266-394; Coverage: 56%)
  • Canonical: P63096 (Residues: 4-19, 61-181, 229-242; Coverage: 40%)
Gene names: GNAI1, GNAS, GNAS1, GSP
Sequence domains: G-protein alpha subunit
SAR425899 Chain: P
Molecule details ›
Chain: P
Length: 29 amino acids
Theoretical weight: 3.24 KDa
Source organism: synthetic construct
Expression system: Not provided
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: G
Molecule details ›
Chain: G
Length: 70 amino acids
Theoretical weight: 7.73 KDa
Source organism: Bos taurus
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63212 (Residues: 2-71; Coverage: 99%)
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: Escherichia coli
Expression system: Escherichia coli
Glucagon-like peptide 1 receptor Chain: R
Molecule details ›
Chain: R
Length: 440 amino acids
Theoretical weight: 50.86 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P43220 (Residues: 24-463; Coverage: 100%)
Gene name: GLP1R
Sequence domains:

Ligands and Environments

1 bound ligand:
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 2.57Å
Relevant EMDB volumes: EMD-36325
Expression systems:
  • Spodoptera frugiperda
  • Not provided
  • Escherichia coli