› 6xox

Electron Microscopy
3.1Å resolution

cryo-EM of human GLP-1R bound to non-peptide agonist LY3502970

Released:
DOI: 10.2210/pdb6xox/pdb
PDB entry 6xox coloured by chain, front view.
PDB entry 6xox coloured by chain, side view.
PDB entry 6xox coloured by chain, top view.
Source organisms:
Primary publication:
Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.
Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW
Proc Natl Acad Sci U S A 117 29959-29967 (2020)
PMID: 33177239
Related structures: EMD-22283

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-243167 (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: 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 scFv16 Chain: E
Molecule details ›
Chain: E
Length: 259 amino acids
Theoretical weight: 27.78 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: Trichoplusia ni
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
Glucagon-like peptide 1 receptor Chain: R
Molecule details ›
Chain: R
Length: 445 amino acids
Theoretical weight: 51.23 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P43220 (Residues: 24-422; Coverage: 91%)
Gene name: GLP1R
Sequence domains:

Ligands and Environments

1 bound ligand:
Ligand V6G 1 x V6G
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 3.1Å
Relevant EMDB volumes: EMD-22283
Expression systems:
  • Trichoplusia ni
  • Spodoptera frugiperda
  • Escherichia coli

Quick links

Citations

14 review citations

The therapeutic potential of GLP-1 receptor biased agonism.
Jones B. (2022)
13 more

10 mentions without citation

Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes.
Malik et al. (2022)
9 more