› 7piu

Electron Microscopy
2.58Å resolution

Cryo-EM structure of the agonist setmelanotide bound to the active melanocortin-4 receptor (MC4R) in complex with the heterotrimeric Gs protein at 2.6 A resolution.

Released:
DOI: 10.2210/pdb7piu/pdb
PDB entry 7piu coloured by chain, front view.
PDB entry 7piu coloured by chain, side view.
PDB entry 7piu coloured by chain, top view.
Source organisms:
Primary publication:
Structures of active melanocortin-4 receptor-Gs-protein complexes with NDP-α-MSH and setmelanotide.
Heyder NA, Kleinau G, Speck D, Schmidt A, Paisdzior S, Szczepek M, Bauer B, Koch A, Gallandi M, Kwiatkowski D, Bürger J, Mielke T, Beck-Sickinger AG, Hildebrand PW, Spahn CMT, Hilger D, Schacherl M, Biebermann H, Hilal T, Kühnen P, Kobilka BK, Scheerer P
OpenAccess logo Cell Res 31 1176-1189 (2021)
PMID: 34561620
Related structures: EMD-13453

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-211058 (preferred)
Entry contents:
6 distinct polypeptide molecules
Macromolecules (6 distinct):
Melanocortin receptor 4 Chain: R
Molecule details ›
Chain: R
Length: 346 amino acids
Theoretical weight: 38.7 KDa
Source organism: Homo sapiens
Expression system: Spodoptera aff. frugiperda 1 BOLD-2017
UniProt:
  • Canonical: P32245 (Residues: 1-332; Coverage: 100%)
Gene name: MC4R
Sequence domains: 7 transmembrane receptor (rhodopsin family)
Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree) Chain: P
Molecule details ›
Chain: P
Length: 8 amino acids
Theoretical weight: 1.08 KDa
Source organism: synthetic construct
Expression system: Not provided
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short; Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short Chain: A
Molecule details ›
Chain: A
Length: 380 amino acids
Theoretical weight: 44.33 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P63092 (Residues: 1-394; Coverage: 96%)
  • Best match: P63092-2 (Residues: 1-380)
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: 37.73 KDa
Source organism: Rattus norvegicus
Expression system: Trichoplusia ni
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: 71 amino acids
Theoretical weight: 7.86 KDa
Source organism: Bos taurus
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P63212 (Residues: 1-71; Coverage: 100%)
Gene name: GNG2
Sequence domains: GGL domain
Camelid antibody fragment - nanobody 35 Chain: N
Molecule details ›
Chain: N
Length: 134 amino acids
Theoretical weight: 14.71 KDa
Source organism: Lama glama
Expression system: Escherichia coli

Ligands and Environments

1 bound ligand:
Ligand CA 1 x CA
2 modified residues:
Ligand DAL 1 x DAL
Ligand DPN 1 x DPN

Experiments and Validation Details

Entry percentile scores
Resolution: 2.58Å
Relevant EMDB volumes: EMD-13453
Expression systems:
  • Spodoptera aff. frugiperda 1 BOLD-2017
  • Not provided
  • Trichoplusia ni
  • Escherichia coli

Quick links

Citations

5 review citations

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting.
Speck et al. (2022)
4 more

3 mentions without citation

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.
Wong et al. (2023)
2 more