8ZCF: GPR4

Cryo-EM structure of GPR4 complexed with Gs in pH7.5. Determined by electron microscopy at 2.9 Å resolution. Released 23 Apr 2025.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Homo sapiens, Lama glama
Chains: 5
Atoms: 8,053
Mol. weight: 142.89 kDa
Released: 23 Apr 2025

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

Secondary structure: helices and β-sheets

8ZCF contains 29 α-helices and 50 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	12-39	28
β-strand	40-46	7	1
α-helix	54-60	7
β-strand	207-214	8	1
β-strand	217-224	8	1
α-helix	234-236	3
β-strand	243-246	4	1
α-helix	265-278	14
β-strand	286-289	4	1
α-helix	295-299	5
α-helix	300-304	5
α-helix	313-315	3
α-helix	332-350	19
β-strand	360-361	2	1
α-helix	371-390	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-34	5
α-helix	38-39	2
β-strand	47-52	6	2
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	88-94	7	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
β-strand	134-139	6	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	175-181	7	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	315-320	6	2
β-strand	327-331	5	2
β-strand	335-339	5	2

Chain C: 4 helices, 0 β-strands

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

Chain N: 0 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	9
β-strand	17	1	10
β-strand	22	1	9
β-strand	35-39	5	11
β-strand	46-50	5	11
β-strand	59-60	2	11
β-strand	69	1	12
β-strand	72-73	2	13
β-strand	78-79	2	13
β-strand	82	1	12
β-strand	84	1	10
β-strand	93-95	3	11
β-strand	122-123	2	11

Chain R: 13 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	19-47	29
α-helix	51-78	28
β-strand	82	1	14
α-helix	87-97	11
α-helix	100-120	21
α-helix	131-149	19
α-helix	151-154	4
β-strand	160	1	14
β-strand	166	1	14
α-helix	176-184	9
α-helix	185-191	7
α-helix	192-210	19
α-helix	216-253	38
α-helix	259-275	17
α-helix	278-286	9
α-helix	291-299	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	402	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	340	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	C	protein	71	Homo sapiens	P59768 (AlphaFold model)
Nanobody 35	N	protein	129	Lama glama
G-protein coupled receptor 4	R	protein	323	Homo sapiens	P46093 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8ZCF_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MDYKDDDDKGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESG
KNTIVKQMRILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSN
LVPPVELANPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLI
DCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERR
KWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLN
KQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTAS
GDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>8ZCF_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYA
MHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNI
CSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTF
TGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNA
FATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDAL
KADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (C), FASTA

>8ZCF_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8ZCF_4 Nanobody 35 (chains N)
MQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASIS
YTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRG
QGTQVTVSS

Sequence of entity 5 (R), FASTA

>8ZCF_5 G-protein coupled receptor 4 (chains R)
MGNHTWEGCHVDSRVDHLFPPSLYIFVIGVGLPTNCLALWAAYRQVQQRNELGVYLMNLS
IADLLYICTLPLWVDYFLHHDNWIHGPGSCKLFGFIFYTNIYISIAFLCCISVDRYLAVA
HPLRFARLRRVKTAVAVSSVVWATELGANSAPLFHDELFRDRYNHTFCFEKFPMEGWVAW
MNLYRVFVGFLFPWALMLLSYRGILRAVRGSVSTERQEKAKIKRLALSLIAIVLVCFAPY
HVLLLSRSAIYLGRPWDCGFEERVFSAYHSSLAFTSLNCVADPILYCLVNEGARSDVAKA
LHNLLRFLASDKPQEMANASLTL

Primary citation

Structural basis of stepwise proton sensing-mediated GPCR activation. Yue, X., Peng, L., Liu, S. et al. Cell Res (2025) 35:423-436. DOI 10.1038/s41422-025-01092-w · PubMed

Other PDB entries of the same protein (UniProt P63092 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7BPH 1.57 Å, Crystal structure of GppNHp-bound GNAS in complex with the cyclic peptide inhibitor GN13
6AU6 1.7 Å, Crystal structure of GDP-bound human GNAS R201C mutant
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
7E5E 1.95 Å, Crystal structure of GDP-bound GNAS in complex with the cyclic peptide inhibitor GD20
7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
8F0J 2.0 Å, Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
9XXT 2.0 Å, Cryo-EM structure of lysophosphatidylserine (18:0)-bound GPR174-Gs complex
6X18 2.1 Å, GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
6X19 2.1 Å, Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
9NTU 2.1 Å, Cryo-EM structure of BETP-GLP-1(9-36)-GLP-1R-Gs complex
7RTB 2.14 Å, Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)

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