7F58: THIQ-MC4R-Gs_Nb35 complex
Cryo-EM structure of THIQ-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
- 5
- Atoms
- 8,065
- Mol. weight
- 164.27 kDa
- Ligands
- CA, 1I8
- Released
- 3 Nov 2021
Explore 7F58 in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
7F58 contains 31 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 | 53-59 | 7 | |
| 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 | 4-24 | 21 | |
| α-helix | 30-32 | 3 | |
| α-helix | 34-36 | 3 | |
| β-strand | 47-51 | 5 | 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 | 317-320 | 4 | 2 |
| β-strand | 327-330 | 4 | 2 |
| β-strand | 336-339 | 4 | 2 |
Chain G: 4 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| 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 | 34-39 | 6 | 10 |
| β-strand | 46-51 | 6 | 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: 11 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 48-70 | 23 | |
| α-helix | 78-109 | 32 | |
| α-helix | 118-152 | 35 | |
| α-helix | 157-160 | 4 | |
| α-helix | 163-186 | 24 | |
| α-helix | 191-227 | 37 | |
| α-helix | 239-270 | 32 | |
| α-helix | 275-281 | 7 | |
| α-helix | 284-301 | 18 | |
| α-helix | 303-305 | 3 | |
| α-helix | 307-319 | 13 | |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| Melanocortin receptor 4 | R | protein | 507 | Homo sapiens | P32245 (AlphaFold model) |
| 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 | |
Sequence of entity 1 (R), FASTA
>7F58_1 Melanocortin receptor 4 (chains R)
GPMVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVIS
LLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFT
VNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACT
VSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQG
ANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIID
PLIYALRSQELRKTFKEIICCYPLGGLCDLSSRYGGSGGSVFTLEDFVGDWEQTAAYNLD
QVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKV
VYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIID
ERLITPDGSMLFRVTINSGGSLEVLFQ
Sequence of entity 2 (A), FASTA
>7F58_2 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 3 (B), FASTA
>7F58_3 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 4 (G), FASTA
>7F58_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL
Sequence of entity 5 (N), FASTA
>7F58_5 Nanobody35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTV
Ligands and cofactors
| ID | Name | Formula | Copies |
|---|
| CA | Calcium ion | Ca | 1 |
| 1I8 | (3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)pip… | C33 H41 Cl N6 O2 | 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 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
- 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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