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7PIU

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.

Entity
Entity IDChain IDDescriptionTypeChain lengthFormula weightNumber of moleculesDB Name (Accession)Biological sourceDescriptive keywords
1A
(R)
Melanocortin receptor 4polymer34638698.51UniProt (P32245)
Pfam (PF00001)
Homo sapiens (Human)MC4-R
2B
(P)
Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree)polymer81081.31synthetic construct
3C
(A)
Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortpolymer38044326.21UniProt (P63092)
Pfam (PF00503)
Homo sapiens (Human)Adenylate cyclase-stimulating G alpha protein
4D
(B)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1polymer34537728.21UniProt (P54311)
Pfam (PF00400)
Rattus norvegicus (Rat)Transducin beta chain 1
5E
(G)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2polymer717861.11UniProt (P63212)
Pfam (PF00631)
Bos taurus (Bovine)G gamma-I
6F
(N)
Camelid antibody fragment - nanobody 35polymer13414714.31Lama glama
7G
(R)
CALCIUM IONnon-polymer40.11Chemie (CA)
8H, I, J, K, L...
(R, P, A, B, G...)
waterwater18.088Chemie (HOH)
Sequence modifications
R: 1 - 332 (UniProt: P32245)
PDBExternal DatabaseDetails
Asp -7-expression tag
Tyr -6-expression tag
Lys -5-expression tag
Asp -4-expression tag
Asp -3-expression tag
Asp -2-expression tag
Asp -1-expression tag
Lys 0-expression tag
Leu 333-expression tag
Glu 334-expression tag
Val 335-expression tag
Leu 336-expression tag
Phe 337-expression tag
Gln 338-expression tag
B: 2 - 340 (UniProt: P54311)
PDBExternal DatabaseDetails
Gly -4-expression tag
Pro -3-expression tag
Gly -2-expression tag
Ser -1-expression tag
Ser 0-expression tag
Gly 1-expression tag
Sequence viewer
Contents of the asymmetric unit
PolymersNumber of chains6
Total formula weight144409.6
Non-Polymers*Number of molecules1
Total formula weight40.1
All*Total formula weight144449.7
*Water molecules are not included.

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PDB entries from 2026-01-14

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