7W2Z: Ghrelin-bound human ghrelin receptor-Go complex

Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex. Determined by electron microscopy at 2.8 Å resolution. Released 19 Jan 2022.

Method: Electron microscopy
Resolution: 2.8 Å
Organisms: Homo sapiens, synthetic construct
Chains: 6
Atoms: 9,080
Mol. weight: 142.35 kDa
Ligands: CLR
Released: 19 Jan 2022

Explore 7W2Z in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7W2Z contains 37 α-helices and 63 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: 7 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-38	5	1
β-strand	55	1	1
β-strand	186-191	6	1
β-strand	196-201	6	1
α-helix	209-212	4
α-helix	213-216	4
β-strand	221-227	7	1
α-helix	244-255	12
β-strand	264-270	7	1
α-helix	272-281	10
α-helix	297-309	13
β-strand	319-322	4	1
α-helix	331-350	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	9
β-strand	58-63	6	10
β-strand	69-74	6	10
β-strand	78-83	6	10
β-strand	88-94	7	10
β-strand	100-105	6	11
β-strand	111-116	6	11
β-strand	121-125	5	11
β-strand	134-139	6	11
β-strand	146-151	6	12
β-strand	156-161	6	12
β-strand	165-170	6	12
β-strand	175-181	7	12
β-strand	187-192	6	13
β-strand	199-203	5	13
β-strand	208-211	4	13
β-strand	218-222	5	13
β-strand	229-234	6	14
β-strand	240-245	6	14
β-strand	249-254	6	14
β-strand	259-264	6	14
β-strand	273-278	6	15
β-strand	284-289	6	15
β-strand	294-298	5	15
β-strand	304-308	5	15
β-strand	315-320	6	9
β-strand	327-331	5	9
β-strand	336-339	4	9

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	11-21	11
α-helix	27-29	3
α-helix	30-43	14
α-helix	53-55	3

Chain L: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	9-13	5

Chain R: 16 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	40-70	31
α-helix	72-74	3
α-helix	77-94	18
α-helix	96-104	9
α-helix	115-146	32
α-helix	160-174	15
α-helix	178-181	4
β-strand	182-185	4	2
β-strand	197-200	4	2
α-helix	202-207	6
α-helix	209-217	9
α-helix	219-239	21
α-helix	253-280	28
α-helix	282-288	7
α-helix	300-303	4
α-helix	307-314	8
α-helix	319-322	4
α-helix	328-338	11

Chain S: 6 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	3
β-strand	11-12	2	4
β-strand	17-25	9	3
α-helix	29-31	3
β-strand	33-39	7	5
β-strand	45-51	7	5
β-strand	58-60	3	5
β-strand	65	1	3
β-strand	68-73	6	3
β-strand	78-84	7	3
α-helix	88-90	3
β-strand	92-99	8	5
β-strand	110-111	2	5
β-strand	115-117	3	5
β-strand	118-119	2	4
β-strand	128-129	2	6
β-strand	134-136	3	7
β-strand	143-149	7	6
β-strand	154	1	8
β-strand	160	1	8
β-strand	162-167	6	7
β-strand	173-178	6	7
β-strand	182-183	2	7
α-helix	184	1
β-strand	191-195	5	6
β-strand	199-204	6	6
α-helix	209-211	3
β-strand	214-219	6	7
α-helix	225	1
β-strand	227	1	7
α-helix	228-230	3
β-strand	231-234	4	7

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(o) subunit alpha	A	protein	236	Homo sapiens	P09471 (AlphaFold model)
Growth hormone secretagogue receptor type 1	R	protein	366	Homo sapiens	Q92847 (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	250	synthetic construct
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	339	Homo sapiens	P62873 (AlphaFold model)
Appetite-regulating hormone	L	protein	16	Homo sapiens	Q9UBU3

Sequence of entity 1 (A), FASTA

>7W2Z_1 Guanine nucleotide-binding protein G(o) subunit alpha (chains A)
MTLSAEERAALERSKAIEKNLKEDGISAAKDVKLLLLGADNSGKSTIVKQMKIIHGGSGG
SGGTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVDLSDYDQVLHED
ETTNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYE
DAAAYIQAQFESKNRSPNKEIYCHMTCATDTNNAQVIFDAVTDIIIANNLRGCGLY

Sequence of entity 2 (R), FASTA

>7W2Z_2 Growth hormone secretagogue receptor type 1 (chains R)
MWNATPSEEPGFNLTLADLDWDASPGNDSLGDELLQLFPAPLLAGVTATCVALFVVGIAG
NLLTMLVVSRFRELRTTTNLYLSSMAFSDLLIFLCMPLDLVRLWQYRPWNFGDLLCKLFQ
FVSESCTYATVLTITALSVERYFAICFPLRAKVVVTKGRVKLVIFVIWAVAFCSAGPIFV
LVGVEHENGTDPWDTNECRPTEFAVRSGLLTVMVWVSSIFFFLPVFCLTVLYSLIGRKLW
RRRRGDAVVGASLRDQNHKQTVKMLAVVVFAFILCWLPFHVGRYLFSKSFEPGSLEIAQI
SQYCNLVSFVLFYLSAAINPILYNIMSKKYRVAVFRLLGFEPFSQRKLSTLKDESSRAWT
ESSINT

Sequence of entity 3 (G), FASTA

>7W2Z_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (S), FASTA

>7W2Z_4 ScFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGS

Sequence of entity 5 (B), FASTA

>7W2Z_5 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
SELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAM
HWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNIC
SIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFT
GHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAF
ATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALK
ADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 6 (L), FASTA

>7W2Z_6 Appetite-regulating hormone (chains L)
GSXFLSPEHQRVQQRK

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	2

Primary citation

Molecular mechanism of agonism and inverse agonism in ghrelin receptor. Qin, J., Cai, Y., Xu, Z. et al. Nat Commun (2022) 13:300-300. DOI 10.1038/s41467-022-27975-9 · PubMed

Other PDB entries of the same protein (UniProt P09471 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9BSB 2.32 Å, Global reconstruction of DRD2 bound to LSD in complex with a mini-GoA and scFv16…
9VJE 2.47 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with buspirone
9K20 2.65 Å, Cryo-EM structure of ATP-bound P2Y purinoceptor 2-miniGo-scFv16 complex
9VJ5 2.69 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with gepirone
8E9X 2.7 Å, CryoEM structure of miniGo-coupled hM4Di in complex with DCZ
9T88 2.74 Å, Cryo-EM structure of ESG-2-37-bound D3 dopamine receptor with mini-Go
9VNF 2.74 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with (S)-pindolol
8YN7 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with immethridine and miniGo
8YN8 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with proxyfan and miniGo
9KVP 2.79 Å, Structure of SB290157 bound to human C3aR in complex with Go (Full map)
8XXH 2.8 Å, Structure of CXCR2 bound to CXCL2 (CXCR2-CXCL2-Go Full map)
9PLO 2.8 Å, Structure of alpha2a adrenergic receptor in complex with Go heterotrimer, scFv16, and…

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