8W8W: Alpha-MSH-MC3R-Gs_Nb35 complex

Cryo-EM structure of alpha-MSH-MC3R-Gs_Nb35 complex. Determined by electron microscopy at 2.9 Å resolution. Released 19 Mar 2025.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Escherichia coli, Homo sapiens, Rattus norvegicus
Chains: 6
Atoms: 7,642
Mol. weight: 179.99 kDa
Ligands: CA
Released: 19 Mar 2025

Explore 8W8W in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8W8W contains 22 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: 6 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	16-38	23
β-strand	41-44	4	10
β-strand	209-214	6	10
β-strand	217-222	6	10
α-helix	235-237	3
β-strand	243-248	6	10
α-helix	265-277	13
β-strand	286-291	6	10
α-helix	313-317	5
α-helix	332-349	18
β-strand	359-363	5	10
α-helix	371-390	20

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
β-strand	47-51	5	1
β-strand	58-63	6	2
β-strand	69-74	6	2
β-strand	78-83	6	2
β-strand	89-94	6	2
β-strand	100-105	6	3
β-strand	111-116	6	3
β-strand	121-125	5	3
β-strand	134-139	6	3
β-strand	146-151	6	4
β-strand	156-161	6	4
β-strand	166-170	5	4
β-strand	175-180	6	4
β-strand	187-192	6	5
β-strand	198-203	6	5
β-strand	208-212	5	5
β-strand	217-222	6	5
β-strand	229-234	6	6
β-strand	240-245	6	6
β-strand	250-254	5	6
β-strand	259-264	6	6
β-strand	273-278	6	7
β-strand	284-289	6	7
β-strand	294-298	5	7
β-strand	303-308	6	7
β-strand	315-320	6	1
β-strand	327-331	5	1
β-strand	336-339	4	1

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
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	8
β-strand	10-11	2	9
β-strand	18-25	8	8
α-helix	29-31	3
β-strand	34-39	6	9
β-strand	45-51	7	9
β-strand	58-60	3	9
β-strand	68-73	6	8
β-strand	78-83	6	8
α-helix	88-90	3
β-strand	92-98	7	9
β-strand	118	1	9
β-strand	122-125	4	9

Chain R: 8 helices, 0 β-strands

Element	Residues	Length
α-helix	42-64	23
α-helix	72-100	29
α-helix	112-147	36
α-helix	158-181	24
α-helix	190-221	32
α-helix	239-267	29
α-helix	281-298	18
α-helix	304-309	6

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Soluble cytochrome b562,Melanocortin receptor 3,Fusion protein	R	protein	602	Escherichia coli, Homo sapiens	P41968 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	384	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Bos taurus	P63212 (AlphaFold model)
Nanobody35	N	protein	160	Lama glama
alpha-MSH	L	protein	13	Homo sapiens	P01189 (AlphaFold model)
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	380	Homo sapiens	P63092

Sequence of entity 1 (R), FASTA

>8W8W_1 Soluble cytochrome b562,Melanocortin receptor 3,Fusion protein (chains R)
DYKDDDDKGSADLEDNWETLNDNLKVIEKADNAAQVKDALTKMRAAALDAQKATPPKLED
KSPDSPEMKDFRHGFDILVGQIDDALKLANEGKVKEAQAAAEQLKTTRNAYIQKYLLVPR
GSNASCCLPSVQPTLPNGSEHLQAPFFSNQSSSAFCEQVFIKPEVFLSLGIVSLLENILV
ILAVVRNGNLHSPMYFFLCSLAVADMLVSVSNALETIMIAIVHSDYLTFEDQFIQHMDNI
FDSMICISLVASICNLLAIAVDRYVTIFYALRYHSIMTVRKALTLIVAIWVCCGVCGVVF
IVYSESKMVIVCLITMFFAMMLLMGTLYVHMFLFARLHVKRIAALPPADGVAPQQHSCMK
GAVTITILLGVFIFCWAPFFLHLVLIITCPTNPYCICYTAHFNTYLVLIMCNSVIDPLIY
AFRSLELRNTFREILCGCNGMNLGVFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLA
VSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKVVYPVDDHHFKVILPYG
TLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLITPDGSMLFRVTI
NS

Sequence of entity 2 (B), FASTA

>8W8W_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

>8W8W_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8W8W_4 Nanobody35 (chains N)
MKYLLPTAAAGLLLLAAQPAMAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVR
QAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCAR
CPAPFTRDCFDVTSTTYAYRGQGTQVTVSSHHHHHHEPEA

Sequence of entity 5 (L), FASTA

>8W8W_5 alpha-MSH (chains L)
SYSMEHFRWGKPV

Sequence of entity 6 (A), FASTA

>8W8W_6 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSV
MNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSD
QDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYN
MVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPE
FARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRR
VFNDCRDIIQRMHLRQYELL

Ligands and cofactors

ID	Name	Formula	Copies
CA	Calcium ion	Ca	1

Primary citation

Structure basis of ligand selectivity and signal transduction in human melanocortin-3 receptor. Jingpeng, F., Hongli, H. To be published.

Other PDB entries of the same protein (UniProt P41968 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9K3F 2.75 Å, Cryo-EM structure of the unliganded human melanocortin receptor 3 (MC3R)-Gs complex
8IOC 2.86 Å, Cryo-EM structure of the gamma-MSH-bound human melanocortin receptor 3 (MC3R)-Gs complex
8W8X 2.9 Å, Cryo-EM structure of beta-MSH-MC3R-Gs_Nb35 complex
8W8Y 2.9 Å, Cryo-EM structure of gamma-MSH-MC3R-Gs_Nb35 complex
8KIG 3.1 Å, Cryo-EM structure of MC3R in complex with SHU9119

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