7F55: Bremelanotide-MC4R-Gs_Nb35 complex

Cryo-EM structure of bremelanotide-MC4R-Gs_Nb35 complex. Determined by electron microscopy at 3.1 Å resolution. Released 3 Nov 2021.

Method: Electron microscopy
Resolution: 3.1 Å
Organisms: Homo sapiens, synthetic construct
Chains: 6
Atoms: 8,088
Mol. weight: 164.68 kDa
Ligands: CA
Released: 3 Nov 2021

Explore 7F55 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7F55 contains 32 α-helices and 45 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: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	13-38	26
β-strand	40-47	8	1
α-helix	53-58	6
β-strand	207-214	8	1
β-strand	217-224	8	1
β-strand	243-249	7	1
α-helix	265-277	13
β-strand	286-292	7	1
α-helix	294-302	9
α-helix	308-310	3
α-helix	313-317	5
α-helix	326-327	2
α-helix	332-352	21
β-strand	359-363	5	1
α-helix	371-390	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-23	20
α-helix	30-32	3
α-helix	34-36	3
β-strand	47-52	6	2
α-helix	57	1
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	89-94	6	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	120-125	6	4
β-strand	134-140	7	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	166-170	5	5
β-strand	175-180	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	218-223	6	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	293-298	6	8
β-strand	304-309	6	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	9-23	15
α-helix	27-29	3
α-helix	30-43	14
α-helix	45-47	3

Chain N: 3 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-11	2	10
β-strand	18-25	8	9
α-helix	29-31	3
β-strand	34-40	7	10
β-strand	43-51	9	10
β-strand	58-60	3	10
α-helix	62-64	3
β-strand	68-73	6	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	122-125	4	10

Chain R: 12 helices, 0 β-strands

Element	Residues	Length
α-helix	43-44	2
α-helix	48-70	23
α-helix	78-109	32
α-helix	117-152	36
α-helix	157-159	3
α-helix	163-186	24
α-helix	191-227	37
α-helix	239-270	32
α-helix	275-281	7
α-helix	284-297	14
α-helix	298-301	4
α-helix	307-319	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	380	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	384	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)
Nanobody35	N	protein	126	synthetic construct
Melanocortin receptor 4	R	protein	507	Homo sapiens	P32245 (AlphaFold model)
bremelanotide	L	protein	7	synthetic construct

Sequence of entity 1 (A), FASTA

>7F55_1 Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSV
MNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSD
QDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVASSSYN
MVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEKVLAGKSKIEDYFPE
FARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRR
VFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>7F55_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGS
SGGGGSGGGGSSGVSGWRLFKKIS

Sequence of entity 3 (G), FASTA

>7F55_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>7F55_4 Nanobody35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTV

Sequence of entity 5 (R), FASTA

>7F55_5 Melanocortin receptor 4 (chains R)
GPMVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVIS
LLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFT
VNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACT
VSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQG
ANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIID
PLIYALRSQELRKTFKEIICCYPLGGLCDLSSRYGGSGGSVFTLEDFVGDWEQTAAYNLD
QVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKV
VYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIID
ERLITPDGSMLFRVTINSGGSLEVLFQ

Sequence of entity 6 (L), FASTA

>7F55_6 bremelanotide (chains L)
LDHFRWK

Ligands and cofactors

ID	Name	Formula	Copies
CA	Calcium ion	Ca	1

Primary citation

Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Zhang, H., Chen, L.N., Yang, D. et al. Cell Res (2021) 31:1163-1175. DOI 10.1038/s41422-021-00552-3 · PubMed

Other PDB entries of the same protein (UniProt P63092 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7BPH 1.57 Å, Crystal structure of GppNHp-bound GNAS in complex with the cyclic peptide inhibitor GN13
6AU6 1.7 Å, Crystal structure of GDP-bound human GNAS R201C mutant
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
7E5E 1.95 Å, Crystal structure of GDP-bound GNAS in complex with the cyclic peptide inhibitor GD20
7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
8F0J 2.0 Å, Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
9XXT 2.0 Å, Cryo-EM structure of lysophosphatidylserine (18:0)-bound GPR174-Gs complex
6X18 2.1 Å, GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
6X19 2.1 Å, Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
9NTU 2.1 Å, Cryo-EM structure of BETP-GLP-1(9-36)-GLP-1R-Gs complex
7RTB 2.14 Å, Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)

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