9K3K: PDB entry 9K3K

Cryo-EM structure of the unliganded human melanocortin receptor 4 (MC4R)-Gs complex. Determined by electron microscopy at 3.12 Å resolution. Released 6 Aug 2025.

Method: Electron microscopy
Resolution: 3.12 Å
Organisms: Homo sapiens, synthetic construct, Bos taurus
Chains: 6
Atoms: 9,755
Mol. weight: 193.25 kDa
Released: 6 Aug 2025

Explore 9K3K in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9K3K contains 37 α-helices and 67 β-strands across 6 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 10 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	14-38	25
β-strand	40-47	8	1
α-helix	53-62	10
β-strand	207-214	8	1
β-strand	217-224	8	1
α-helix	236-238	3
β-strand	243-249	7	1
α-helix	266-278	13
β-strand	286-292	7	1
α-helix	294-302	9
α-helix	308-310	3
α-helix	313-315	3
α-helix	326-327	2
α-helix	332-351	20
β-strand	359-360	2	1
β-strand	363	1	1
α-helix	371-390	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
α-helix	30-33	4
α-helix	38-40	3
β-strand	49-52	4	2
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	88-94	7	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
β-strand	134-139	6	4
β-strand	146-151	6	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	175-180	6	5
β-strand	191-192	2	6
β-strand	198-202	5	6
β-strand	208-212	5	6
β-strand	218-222	5	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	259-264	6	7
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	304-308	5	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	335-339	5	2

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-44	15
α-helix	45-47	3
α-helix	53-55	3

Chain N: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-12	3	10
β-strand	18-25	8	9
α-helix	29-31	3
β-strand	34-39	6	10
β-strand	46-51	6	10
β-strand	58-60	3	10
β-strand	69-73	5	9
β-strand	78-83	6	9
α-helix	88-90	3
β-strand	92-98	7	10
β-strand	118	1	10
β-strand	122-126	5	10

Chain R: 13 helices, 0 β-strands

Element	Residues	Length
α-helix	48-71	24
α-helix	78-106	29
α-helix	131-152	22
α-helix	154-160	7
α-helix	164-183	20
α-helix	195-227	33
α-helix	239-256	18
α-helix	259-270	12
α-helix	275-281	7
α-helix	284-294	11
α-helix	298	1
α-helix	299-303	5
α-helix	307-315	9

Chain S: 5 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	10-12	3	12
β-strand	18-25	8	11
β-strand	33-39	7	12
β-strand	45-51	7	12
β-strand	58-60	3	12
α-helix	62-64	3
β-strand	68-73	6	11
α-helix	74-76	3
β-strand	78-83	6	11
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	110-111	2	12
β-strand	115-119	5	12
β-strand	141	1	13
β-strand	146-148	3	14
β-strand	155-160	6	13
β-strand	174-179	6	14
β-strand	186-190	5	14
β-strand	194-195	2	14
β-strand	203-207	5	13
β-strand	211-216	6	13
α-helix	221-223	3
β-strand	225-231	7	14
α-helix	237	1
β-strand	243-246	4	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Melanocortin receptor 4,Melanocortin receptor 4,Melanocortin receptor 4,LgBiT subunit	R	protein	505	Homo sapiens, synthetic construct	P32245 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s)…	A	protein	361	Homo sapiens	P63092 (AlphaFold model), P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,Guanine nucleotide-binding…	B	protein	371	Homo sapiens, synthetic construct	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Bos taurus	P63212
Nb35	N	protein	160	synthetic construct
scFv16	S	protein	285	synthetic construct

Sequence of entity 1 (R), FASTA

>9K3K_1 Melanocortin receptor 4,Melanocortin receptor 4,Melanocortin receptor 4,LgBiT subunit (chains R)
MVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLL
ENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVN
IDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVS
GILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGAN
MKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPL
IYALRSQELRKTFKEIICCYPLGGLCDLSSRYGSSGGGGSGGGGSSGVFTLEDFVGDWEQ
TAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQ
IEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLW
NGNKIIDERLITPDGSMLFRVTINS

Sequence of entity 2 (A), FASTA

>9K3K_2 Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHLRQYEL
L

Sequence of entity 3 (B), FASTA

>9K3K_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,HiBiT (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGGGGSSG
VSGWRLFKKIS

Sequence of entity 4 (G), FASTA

>9K3K_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (N), FASTA

>9K3K_5 Nb35 (chains N)
MKYLLPTAAAGLLLLAAQPAMAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVR
QAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCAR
CPAPFTRDCFDVTSTTYAYRGQGTQVTVSSHHHHHHEPEA

Sequence of entity 6 (S), FASTA

>9K3K_6 scFv16 (chains S)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFAVQLVESGGGLVQPGGSRKLSCS
ASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQM
TSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSAGGGGSGGGGSGGGGSADIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLEL

Primary citation

Structural basis for the constitutive activity of the melanocortin receptor family. Feng, W., Zhou, Q., Zheng, C. et al. Structure (2025) 33:1074-1087.e5. DOI 10.1016/j.str.2025.03.004 · PubMed

Other PDB entries of the same protein (UniProt P32245 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7PIU 2.58 Å, Cryo-EM structure of the agonist setmelanotide bound to the active melanocortin-4…
6W25 2.75 Å, Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with SHU9119
7PIV 2.86 Å, Active Melanocortin-4 receptor (MC4R)- Gs protein complex bound to agonist NDP-alpha-MSH…
8WKY 2.9 Å, Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with S25
7AUE 2.97 Å, Melanocortin receptor 4 (MC4R) Gs protein complex
7F53 3.0 Å, Cryo-EM structure of a-MSH-MC4R-Gs_Nb35 complex
7F54 3.0 Å, Cryo-EM structure of afamelanotide-MC4R-Gs_Nb35 complex
7F55 3.1 Å, Cryo-EM structure of bremelanotide-MC4R-Gs_Nb35 complex
7F58 3.1 Å, Cryo-EM structure of THIQ-MC4R-Gs_Nb35 complex
21LT 3.11 Å, Cryo-EM structure of the setmelanotide-bound human melanocortin receptor 4 (MC4R)-Gq…
8WKZ 3.3 Å, Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with S31
8QJ2 3.4 Å, Structure of active state MC4R in complex with a potent ligand mimicking nanobody

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