8Z9P: Human GPR4-Gi complex

Cryo-EM structure of human GPR4-Gi complex. Determined by electron microscopy at 2.5 Å resolution. Released 9 Jul 2025.

Method: Electron microscopy
Resolution: 2.5 Å
Organisms: Rattus norvegicus, Bos taurus, Homo sapiens
Chains: 5
Atoms: 9,151
Mol. weight: 148.1 kDa
Ligands: CLR
Released: 9 Jul 2025

Explore 8Z9P in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8Z9P contains 46 α-helices and 63 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: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-23	21
α-helix	30-33	4
α-helix	34-36	3
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	88-94	7	2
β-strand	100-105	6	3
β-strand	111-116	6	3
β-strand	120-125	6	3
β-strand	134-140	7	3
β-strand	146-153	8	4
β-strand	156-161	6	4
β-strand	166-170	5	4
β-strand	176-180	5	4
β-strand	187-192	6	5
β-strand	198-203	6	5
β-strand	207-212	6	5
β-strand	217-223	7	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
α-helix	272	1
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: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-32	26
β-strand	34-40	7	9
α-helix	46-52	7
β-strand	185-191	7	9
β-strand	194-200	7	9
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-225	6	9
α-helix	227-231	5
β-strand	233-234	2	10
β-strand	237-241	5	10
α-helix	242-254	13
β-strand	263-268	6	9
α-helix	271-277	7
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	9
α-helix	331-350	20

Chain G: 6 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	27-29	3
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3
α-helix	56-58	3

Chain R: 17 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	19-47	29
α-helix	51-53	3
α-helix	54-78	25
β-strand	82	1	8
α-helix	88-120	33
α-helix	126-128	3
α-helix	131-148	18
α-helix	151-154	4
β-strand	158-160	3	8
β-strand	166-168	3	8
α-helix	176-184	9
α-helix	185-191	7
α-helix	192-209	18
α-helix	216-253	38
α-helix	259-262	4
α-helix	265-274	10
α-helix	275-277	3
α-helix	278-283	6
α-helix	284-288	5
α-helix	291-309	19

Chain S: 8 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	10-12	3	12
β-strand	18-25	8	11
α-helix	29-31	3
β-strand	33-39	7	12
β-strand	45-51	7	12
α-helix	53-55	3
β-strand	58-60	3	12
β-strand	68-73	6	11
α-helix	74-76	3
β-strand	78-83	6	11
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	110-111	2	12
β-strand	115-119	5	12
α-helix	137-139	3
β-strand	140-141	2	13
β-strand	146-148	3	14
β-strand	155-161	7	13
β-strand	166	1	15
β-strand	172	1	15
β-strand	174-179	6	14
β-strand	186-190	5	14
β-strand	194-195	2	14
α-helix	196	1
β-strand	203-208	6	13
β-strand	211-216	6	13
α-helix	221-223	3
β-strand	226-231	6	14
α-helix	237	1
β-strand	238-239	2	14
β-strand	243-246	4	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	345	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	70	Bos taurus	P63212 (AlphaFold model)
G-protein coupled receptor 4	R	protein	303	Homo sapiens	P46093 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	C	protein	354	Homo sapiens	P63096 (AlphaFold model)
single Fab chain (svFv16)	S	protein	250	synthetic construct

Sequence of entity 1 (B), FASTA

>8Z9P_1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 2 (G), FASTA

>8Z9P_2 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL

Sequence of entity 3 (R), FASTA

>8Z9P_3 G-protein coupled receptor 4 (chains R)
GCHVDSRVDHLFPPSLYIFVIGVGLPTNCLALWAAYRQVQQRNELGVYLMNLSIADLLYI
CTLPLWVDYFLHHDNWIHGPGSCKLFGFIFYTNIYISIAFLCCISVDRYLAVAHPLRFAR
LRRVKTAVAVSSVVWATELGANSAPLFHDELFRDRYNHTFCFEKFPMEGWVAWMNLYRVF
VGFLFPWALMLLSYRGILRAVRGSVSTERQEKAKIKRLALSLIAIVLVCFAPYHVLLLSR
SAIYLGRPWDCGFEERVFSAYHSSLAFTSLNCVADPILYCLVNEGARSDVAKALHNLLRF
LAS

Sequence of entity 4 (C), FASTA

>8Z9P_4 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains C)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 5 (S), FASTA

>8Z9P_5 single Fab chain (svFv16) (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGS

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
8Z9O 2.4 Å, Cryo-EM structure of human GPR4-Gs 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

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