› 8fx5

Electron Microscopy
2.45Å resolution

Human M4 muscarinic acetylcholine receptor complex with Gi1 and xanomeline

Released:
DOI: 10.2210/pdb8fx5/pdb
PDB entry 8fx5 coloured by chain, front view.
PDB entry 8fx5 coloured by chain, side view.
PDB entry 8fx5 coloured by chain, top view.
Source organisms:
Primary publication:
Xanomeline displays concomitant orthosteric and allosteric binding modes at the M4 mAChR.
Burger WAC, Pham V, Vuckovic Z, Powers AS, Mobbs JI, Laloudakis Y, Glukhova A, Wootten D, Tobin AB, Sexton PM, Paul SM, Felder CC, Danev R, Dror RO, Christopoulos A, Valant C, Thal DM
OpenAccess logo Nat Commun 14 5440 (2023)
PMID: 37673901
Related structures: EMD-29524

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:

Structure analysis Details

Assembly composition:
hetero pentamer (preferred)
PDBe Complex ID:
PDB-CPX-228430 (preferred)
Entry contents:
5 distinct polypeptide molecules
Macromolecules (5 distinct):
Muscarinic acetylcholine receptor M4 Chain: R
Molecule details ›
Chain: R
Length: 349 amino acids
Theoretical weight: 39.6 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P08173 (Residues: 1-479; Coverage: 70%)
Gene name: CHRM4
Sequence domains: 7 transmembrane receptor (rhodopsin family)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 Chain: B
Molecule details ›
Chain: B
Length: 349 amino acids
Theoretical weight: 38.4 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: 70 amino acids
Theoretical weight: 7.73 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P59768 (Residues: 2-71; Coverage: 99%)
Gene name: GNG2
Sequence domains: GGL domain
Antibody fragment scFv16 Chain: H
Molecule details ›
Chain: H
Length: 248 amino acids
Theoretical weight: 26.47 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
Guanine nucleotide-binding protein G(i) subunit alpha-1 Chain: A
Molecule details ›
Chain: A
Length: 354 amino acids
Theoretical weight: 40.41 KDa
Source organism: Mus musculus
Expression system: Trichoplusia ni
UniProt:
  • Canonical: B2RSH2 (Residues: 1-354; Coverage: 100%)
Gene names: Gnai-1, Gnai1
Sequence domains: G-protein alpha subunit

Ligands and Environments

1 bound ligand:
Ligand XNO 2 x XNO
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 2.45Å
Relevant EMDB volumes: EMD-29524
Expression systems:
  • Spodoptera frugiperda
  • Trichoplusia ni

Quick links

Citations

1 citations in other articles

Antipsychotic displays dual GPCR binding mode.
Crunkhorn S. (2023)

1 mention without citation

Xanomeline displays concomitant orthosteric and allosteric binding modes at the M4 mAChR.
Burger et al. (2023)