7AUE: Melanocortin receptor 4

Melanocortin receptor 4 (MC4R) Gs protein complex. Determined by electron microscopy at 2.97 Å resolution. Released 28 Apr 2021.

Method: Electron microscopy
Resolution: 2.97 Å
Organisms: Homo sapiens, Mus musculus, synthetic construct
Chains: 6
Atoms: 8,755
Mol. weight: 157.8 kDa
Ligands: CA
Released: 28 Apr 2021

Explore 7AUE in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7AUE contains 39 α-helices and 61 β-strands across 5 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: 11 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	7-27	21
β-strand	34-38	5	1
α-helix	46-54	9
β-strand	186-193	8	1
β-strand	196-203	8	1
α-helix	214-216	3
β-strand	222-228	7	1
α-helix	246-256	11
α-helix	259-261	3
β-strand	265-271	7	1
α-helix	273-280	8
α-helix	287-290	4
α-helix	298-300	3
α-helix	305-306	2
α-helix	311-328	18
β-strand	338-339	2	1
β-strand	342	1	1
α-helix	352-369	18

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	28-36	9
α-helix	47-50	4
β-strand	66-69	4	2
β-strand	75-80	6	3
β-strand	86-91	6	3
β-strand	95-100	6	3
β-strand	105-111	7	3
β-strand	120-122	3	4
β-strand	128-131	4	4
β-strand	138-142	5	4
β-strand	151-156	6	4
β-strand	163-168	6	5
β-strand	173-178	6	5
β-strand	183-187	5	5
β-strand	192-197	6	5
β-strand	204-209	6	6
β-strand	215-220	6	6
β-strand	225-229	5	6
β-strand	235-239	5	6
β-strand	246-251	6	7
β-strand	257-262	6	7
β-strand	267-271	5	7
β-strand	276-281	6	7
α-helix	289	1
β-strand	290-295	6	8
β-strand	301-306	6	8
β-strand	311-315	5	8
β-strand	320-324	5	8
β-strand	332-337	6	2
β-strand	344-348	5	2
β-strand	352-355	4	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	11-19	9
α-helix	30-43	14
α-helix	53-55	3

Chain R: 18 helices, 0 β-strands

Element	Residues	Length
α-helix	48-50	3
α-helix	57-71	15
α-helix	73-75	3
α-helix	78-95	18
α-helix	98-107	10
α-helix	118-121	4
α-helix	125-152	28
α-helix	163-185	23
α-helix	194-202	9
α-helix	205-214	10
α-helix	221-224	4
α-helix	243-250	8
α-helix	252-270	19
α-helix	275-280	6
α-helix	281-286	6
α-helix	289-298	10
α-helix	299-303	5
α-helix	307-314	8

Chain S: 4 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	12	1	10
β-strand	17-25	9	9
α-helix	29-31	3
β-strand	33-39	7	11
β-strand	45-51	7	11
β-strand	58-60	3	11
β-strand	68-73	6	9
α-helix	74-76	3
β-strand	78-84	7	9
β-strand	92-94	3	12
β-strand	95-99	5	11
β-strand	110-111	2	11
β-strand	115-117	3	12
β-strand	119	1	10
α-helix	125-127	3
β-strand	128-129	2	13
β-strand	134-136	3	14
β-strand	143-149	7	13
β-strand	154	1	15
β-strand	160	1	15
β-strand	162-167	6	14
β-strand	174-178	5	14
β-strand	182-183	2	14
β-strand	191-196	6	13
β-strand	199-204	6	13
β-strand	214-219	6	14
α-helix	225	1
β-strand	227	1	14
β-strand	231-234	4	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Melanocortin receptor 4	R	protein	350	Homo sapiens	P32245 (AlphaFold model)
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	373	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	357	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
scFv16	S	protein	256	Mus musculus
Aminoserine	C	protein	9	synthetic construct

Sequence of entity 1 (R), FASTA

>7AUE_1 Melanocortin receptor 4 (chains R)
MVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLL
ENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVN
IDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVS
GILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGAN
MKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPL
IYALRSQELRKTFKEIICCYPLGGLCDLSSRYLEVLFQGPSGSGHHHHHH

Sequence of entity 2 (A), FASTA

>7AUE_2 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAATHRLLLLGAGESGKSTIVKQMRILHVNG
FNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFD
FPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCR
VLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDN
QTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTP
EDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRD
IIQRMHLRQYELL

Sequence of entity 3 (B), FASTA

>7AUE_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
HHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRI
QMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTC
AYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGD
TTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFT
GHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGR
LLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (G), FASTA

>7AUE_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (S), FASTA

>7AUE_5 scFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGSLEVLFQ

Sequence of entity 6 (C), FASTA

>7AUE_6 AMINOSERINE (chains C)
XRCAHFRWC

Ligands and cofactors

ID	Name	Formula	Copies
CA	Calcium ion	Ca	1

Primary citation

Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. Israeli, H., Degtjarik, O., Fierro, F. et al. Science (2021) 372:808-814. DOI 10.1126/science.abf7958 · 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
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…
9K3K 3.12 Å, Cryo-EM structure of the unliganded human melanocortin receptor 4 (MC4R)-Gs complex
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

Browse structure collections

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