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Cryo-EM structure of GPR119-Gs Complex with small molecule agonist GSK-1292263

Electron Microscopy
2.82Å resolution
PDB entry 8zrk coloured by chain, front view.
PDB entry 8zrk coloured by chain, side view.
PDB entry 8zrk coloured by chain, top view.
Source organisms:
Assembly composition:
hetero pentamer (preferred)
Entry contents: 5 distinct polypeptide molecules

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Assemblies

Assembly 1 (preferred)
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Multimeric state: hetero pentamer
Accessible surface area: 45415.9 Å2
Buried surface area: 12547.43 Å2
Dissociation area: 1,091.7 Å2
Dissociation energy (ΔGdiss): -2.06 kcal/mol
Dissociation entropy (TΔSdiss): 12.63 kcal/mol
Symmetry number: 1
PDBe Complex ID: PDB-CPX-246061

Macromolecules

Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Chain: A
Length: 394 amino acids
Theoretical weight: 45.7 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P63092 (Residues: 1-394; Coverage: 100%)
Gene names: GNAS, GNAS1, GSP
Pfam: G-protein alpha subunit
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short in PDB entry 8zrk, assembly 1, front view.
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short in PDB entry 8zrk, assembly 1, side view.
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short in PDB entry 8zrk, assembly 1, top view.
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Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Chain: B
Length: 384 amino acids
Theoretical weight: 42.58 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P62873 (Residues: 2-340; Coverage: 100%)
Gene name: GNB1
Pfam: WD domain, G-beta repeat
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 in PDB entry 8zrk, assembly 1, front view.
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 in PDB entry 8zrk, assembly 1, side view.
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 in PDB entry 8zrk, assembly 1, top view.
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Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
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
Pfam: GGL domain
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 in PDB entry 8zrk, assembly 1, front view.
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 in PDB entry 8zrk, assembly 1, side view.
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 in PDB entry 8zrk, assembly 1, top view.
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nanobody35
Chain: N
Length: 157 amino acids
Theoretical weight: 17.06 KDa
Source organism: synthetic construct
Expression system: Escherichia coli
nanobody35 in PDB entry 8zrk, assembly 1, front view.
nanobody35 in PDB entry 8zrk, assembly 1, side view.
nanobody35 in PDB entry 8zrk, assembly 1, top view.
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Glucose-dependent insulinotropic receptor
Chain: R
Length: 369 amino acids
Theoretical weight: 40.76 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q8TDV5 (Residues: 1-335; Coverage: 100%)
Gene name: GPR119
Pfam: 7 transmembrane receptor (rhodopsin family)
Glucose-dependent insulinotropic receptor in PDB entry 8zrk, assembly 1, front view.
Glucose-dependent insulinotropic receptor in PDB entry 8zrk, assembly 1, side view.
Glucose-dependent insulinotropic receptor in PDB entry 8zrk, assembly 1, top view.
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