8Z9O: Human GPR4-Gs complex

Cryo-EM structure of human GPR4-Gs complex. Determined by electron microscopy at 2.4 Å resolution. Released 16 Jul 2025.

Method: Electron microscopy
Resolution: 2.4 Å
Organisms: Rattus norvegicus, Homo sapiens, Bos taurus
Chains: 5
Atoms: 8,279
Mol. weight: 135.84 kDa
Ligands: CLR
Released: 16 Jul 2025

Explore 8Z9O in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8Z9O contains 33 α-helices and 49 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 B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-23	20
α-helix	30-33	4
α-helix	38-39	2
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	207-212	6	5
β-strand	218-223	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 C: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	13-38	26
β-strand	40-46	7	8
β-strand	207-214	8	8
β-strand	217-224	8	8
α-helix	234-238	5
β-strand	243-249	7	8
α-helix	265-277	13
β-strand	286-292	7	8
α-helix	294-302	9
α-helix	308-310	3
α-helix	313-317	5
α-helix	332-351	20
β-strand	355	1	9
β-strand	357	1	9
β-strand	359-363	5	8
α-helix	371-390	20

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	53-55	3

Chain N: 4 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	10-11	2	11
β-strand	17-25	9	10
α-helix	29-31	3
β-strand	34-39	6	11
β-strand	45-51	7	11
β-strand	58-60	3	11
α-helix	62-64	3
β-strand	68-73	6	10
β-strand	78-84	7	10
α-helix	88-90	3
β-strand	92-98	7	11
α-helix	99	1
β-strand	118	1	11
β-strand	122-125	4	11

Chain R: 14 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	19-46	28
α-helix	51-68	18
α-helix	71-78	8
α-helix	87-120	34
α-helix	127-129	3
α-helix	131-148	18
α-helix	151-154	4
β-strand	158-160	3	12
β-strand	166-168	3	12
α-helix	176-186	11
α-helix	187-191	5
α-helix	192-209	18
α-helix	216-253	38
α-helix	260-283	24
α-helix	284-288	5
α-helix	291-309	19

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	338	Rattus norvegicus	P54311 (AlphaFold model)
Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	C	protein	370	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	57	Bos taurus	P63212 (AlphaFold model)
Nanobody-35	N	protein	126	synthetic construct
G-protein coupled receptor 4	R	protein	303	Homo sapiens	P46093 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>8Z9O_1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
ELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMH
WGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICS
IYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTG
HTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFA
TGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKA
DRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 2 (C), FASTA

>8Z9O_2 Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains C)
DQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQMRILHVNGFNG
DSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFDFPP
EFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLT
SGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTN
RLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDA
TPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQ
RMHLRQYELL

Sequence of entity 3 (G), FASTA

>8Z9O_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
TASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFR

Sequence of entity 4 (N), FASTA

>8Z9O_4 Nanobody-35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTV

Sequence of entity 5 (R), FASTA

>8Z9O_5 G-protein coupled receptor 4 (chains R)
GCHVDSRVDHLFPPSLYIFVIGVGLPTNCLALWAAYRQVQQRNELGVYLMNLSIADLLYI
CTLPLWVDYFLHHDNWIHGPGSCKLFGFIFYTNIYISIAFLCCISVDRYLAVAHPLRFAR
LRRVKTAVAVSSVVWATELGANSAPLFHDELFRDRYNHTFCFEKFPMEGWVAWMNLYRVF
VGFLFPWALMLLSYRGILRAVRGSVSTERQEKAKIKRLALSLIAIVLVCFAPYHVLLLSR
SAIYLGRPWDCGFEERVFSAYHSSLAFTSLNCVADPILYCLVNEGARSDVAKALHNLLRF
LAS

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	2

Primary citation

Proton perception and activation of a proton-sensing GPCR. Chen, L.N., Zhou, H., Xi, K. et al. Mol Cell (2025) 85:1640-1657.e8. DOI 10.1016/j.molcel.2025.02.030 · PubMed

Other PDB entries of the same protein (UniProt P54311 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
9EJZ 2.06 Å, Human M5 muscarinic acetylcholine receptor complex with mini-Gq, agonist acetylcholine…
9IJE 2.34 Å, Epinephrine-activated human beta3 adrenergic receptor
8YK0 2.4 Å, Cryo-EM structure of human GPR156-Gi3 complex
22ES 2.43 Å, Gi bound kappa-opioid receptor in complex with difelikefalin
7MBY 2.44 Å, Human Cholecystokinin 1 receptor (CCK1R) Gq chimera (mGsqi) complex
9WG6 2.44 Å, D1R-Gs in complexed with Dopamine/LY3154207/BMSA1/UNC9815
8JIS 2.46 Å, Cryo-EM structure of the GLP-1R/GCGR dual agonist peptide15-bound human GLP-1R-Gs complex
9M0R 2.47 Å, Structure of neuropeptide FF receptor 1 complex with NPVF
8YKV 2.48 Å, Cryo-EM structure of succinate receptor SUCR1 bound to compound 31
9M1O 2.49 Å, Cryo-EM structures of NPFFR2 complex with neuropeptide FF
7DUQ 2.5 Å, Cryo-EM structure of the compound 2 and GLP-1-bound human GLP-1 receptor-Gs complex

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