8QJ2: Active state MC4R

Structure of active state MC4R in complex with a potent ligand mimicking nanobody. Determined by electron microscopy at 3.4 Å resolution. Released 25 Sept 2024.

Method: Electron microscopy
Resolution: 3.4 Å
Organisms: Homo sapiens, Lama glama, Escherichia coli
Chains: 6
Atoms: 8,108
Mol. weight: 201.92 kDa
Released: 25 Sept 2024

Explore 8QJ2 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8QJ2 contains 28 α-helices and 61 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: 14 helices, 0 β-strands

Element	Residues	Length
α-helix	45-47	3
α-helix	53-71	19
α-helix	78-102	25
α-helix	103-105	3
α-helix	123-152	30
α-helix	157-160	4
α-helix	163-186	24
α-helix	194-224	31
α-helix	242-270	29
α-helix	275-280	6
α-helix	281-283	3
α-helix	284-301	18
α-helix	303-305	3
α-helix	307-311	5

Chain B: 6 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	14-38	25
β-strand	40-48	9	1
β-strand	207-213	7	1
β-strand	218-224	7	1
α-helix	234-237	4
β-strand	243-248	6	1
α-helix	265-277	13
β-strand	286-290	5	1
β-strand	291	1	2
α-helix	297-299	3
α-helix	334-350	17
β-strand	359-360	2	1
β-strand	363	1	2
α-helix	371-390	20

Chain C: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	38-39	2
β-strand	47-51	5	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	88-94	7	4
β-strand	102-105	4	5
β-strand	111-115	5	5
β-strand	121-125	5	5
β-strand	135-139	5	5
β-strand	148-151	4	6
β-strand	156-160	5	6
β-strand	166-170	5	6
β-strand	175-180	6	6
β-strand	187-192	6	7
β-strand	198-203	6	7
β-strand	207-212	6	7
β-strand	218-222	5	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	249-254	6	8
β-strand	260-265	6	8
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	294-298	5	9
β-strand	304-308	5	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain D: 2 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	3	1
β-strand	4	1	14
α-helix	5	1
β-strand	20-23	4	15
β-strand	24	1	14
β-strand	33-36	4	16
β-strand	49-52	4	16
β-strand	58	1	16
β-strand	69-70	2	15
β-strand	77-80	4	15
β-strand	95-99	5	16
β-strand	106-108	3	16

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	11-22	12
α-helix	30-42	13
α-helix	45-47	3
α-helix	53-55	3

Chain N: 0 helices, 15 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	11	1	11
β-strand	18-19	2	12
β-strand	21-25	5	10
β-strand	34-39	6	13
β-strand	45-51	7	13
β-strand	59-60	2	13
β-strand	68-69	2	12
β-strand	72-73	2	10
β-strand	78-79	2	10
β-strand	82-83	2	12
β-strand	92-98	7	13
β-strand	118	1	13
β-strand	122-124	3	13
β-strand	125	1	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	B	protein	394	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	350	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)
Nanobody-35	N	protein	138	Lama glama
Soluble cytochrome b562,Melanocortin receptor 4,Red fluorescent protein drFP583	A	protein	729	Escherichia coli, Homo sapiens, Discosoma sp.	P0ABE7 (AlphaFold model), P32245, Q9U6Y8
pN162	D	protein	117	Lama glama

Sequence of entity 1 (B), FASTA

>8QJ2_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains B)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCSVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (C), FASTA

>8QJ2_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
MHHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRT
LRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGN
YVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWD
IETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDIN
AICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYD
DFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>8QJ2_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8QJ2_4 Nanobody-35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSHHHHHHEPEA

Sequence of entity 5 (A), FASTA

>8QJ2_5 Soluble cytochrome b562,Melanocortin receptor 4,Red fluorescent protein drFP583 (chains A)
FADYKDDDDKAADLEDNWETLNDNLKVIEKADNAAQVKDALTKMRAAALDAQKATPPKLE
DKSPDSPEMKDFRHGFDILVGQIDDALKLANEGKVKEAQAAAEQLKTTRNAYIQKYLLEV
LFQGPMVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLG
VISLLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQ
SFTVNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWA
ACTVSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAI
RQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNS
IIDPLIYALRSQELRKTFKEIICCYPLGGLCDLSSRYLEVLFQGPVSKGEEDNMAIIKEF
MRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKA
YVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPS
DGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPG
AYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKHHHHHHHHHHGLNDIFEAQK
IEWHEEPEA

Sequence of entity 6 (D), FASTA

>8QJ2_6 pN162 (chains D)
QVQLVESGGGLVQPGGSLRLSCAASGSAFSLNVMGWYRQTPGNQRALVAEITKDGSTNYA
DSAKGRFTISRDNAKNTVHLQMDSLKPEDTAVYYCKARTGRIVRPLDYWGQGTQVTV

Primary citation

Structure elucidation of a human melanocortin-4 receptor specific orthosteric nanobody agonist. Fontaine, T., Busch, A., Laeremans, T. et al. Nat Commun (2024) 15:7029-7029. DOI 10.1038/s41467-024-50827-7 · 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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