8Z3Y: Of hGPR4-Gs complex in pH6.8

Cryo-EM structure of of hGPR4-Gs complex in pH6.8. Determined by electron microscopy at 3.2 Å resolution. Released 4 Jun 2025.

Method: Electron microscopy
Resolution: 3.2 Å
Organisms: Homo sapiens, synthetic construct
Chains: 5
Atoms: 8,557
Mol. weight: 160.83 kDa
Released: 4 Jun 2025

Explore 8Z3Y in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8Z3Y contains 32 α-helices and 62 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: 8 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-38	25
β-strand	40-47	8	1
α-helix	53-62	10
β-strand	217-223	7	1
β-strand	228-234	7	1
α-helix	245-248	4
β-strand	253-259	7	1
α-helix	266-277	12
β-strand	286-292	7	1
α-helix	294-303	10
α-helix	313-315	3
α-helix	332-349	18
β-strand	359-363	5	1
α-helix	371-390	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	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
α-helix	272	1
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	304-308	5	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	13-23	11
α-helix	30-41	12
α-helix	53-55	3

Chain R: 13 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	19-47	29
α-helix	53-78	26
β-strand	82	1	16
α-helix	87-119	33
α-helix	131-148	18
α-helix	151-154	4
β-strand	160-161	2	16
β-strand	165-166	2	16
α-helix	178-184	7
α-helix	185-190	6
α-helix	191-208	18
α-helix	216-251	36
α-helix	259-274	16
α-helix	275-277	3
α-helix	278-286	9
α-helix	291-302	12

Chain S: 4 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11-12	2	10
β-strand	17-25	9	9
α-helix	29-31	3
β-strand	33-39	7	11
β-strand	45-51	7	11
β-strand	58-60	3	11
β-strand	68-73	6	9
β-strand	78-84	7	9
α-helix	88-90	3
β-strand	92-99	8	11
β-strand	111	1	11
β-strand	115-117	3	11
β-strand	118-119	2	10
β-strand	128-129	2	12
β-strand	134-136	3	13
β-strand	143-145	3	14
β-strand	148-149	2	12
β-strand	154	1	15
β-strand	160	1	15
β-strand	162-167	6	13
β-strand	174-178	5	13
β-strand	182-183	2	13
α-helix	184	1
β-strand	191-196	6	14
β-strand	199-204	6	14
β-strand	213-219	7	13
α-helix	225	1
β-strand	231-234	4	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	361	Homo sapiens
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	377	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	59	Homo sapiens	P59768 (AlphaFold model)
scFv16	S	protein	285	synthetic construct
G-protein coupled receptor 4	R	protein	362	Homo sapiens	P46093 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8Z3Y_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHLRQYEL
L

Sequence of entity 2 (B), FASTA

>8Z3Y_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRR
TLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSG
NYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALW
DIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDI
NAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGY
DDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSG
GGGSSGVSGWRLFKKIS

Sequence of entity 3 (G), FASTA

>8Z3Y_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
NTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFRE

Sequence of entity 4 (S), FASTA

>8Z3Y_4 scFv16 (chains S)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFAVQLVESGGGLVQPGGSRKLSCS
ASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQM
TSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSAGGGGSGGGGSGGGGSADIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLEL

Sequence of entity 5 (R), FASTA

>8Z3Y_5 G-protein coupled receptor 4 (chains R)
MGNHTWEGCHVDSRVDHLFPPSLYIFVIGVGLPTNCLALWAAYRQVQQRNELGVYLMNLS
IADLLYICTLPLWVDYFLHHDNWIHGPGSCKLFGFIFYTNIYISIAFLCCISVDRYLAVA
HPLRFARLRRVKTAVAVSSVVWATELGANSAPLFHDELFRDRYNHTFCFEKFPMEGWVAW
MNLYRVFVGFLFPWALMLLSYRGILRAVRGSVSTERQEKAKIKRLALSLIAIVLVCFAPY
HVLLLSRSAIYLGRPWDCGFEERVFSAYHSSLAFTSLNCVADPILYCLVNEGARSDVAKA
LHNLLRFLASDKPQEMANASLTLETPLTSKRNSTAKAMTGSWAATPPSQGDQVQLKMLPP
AQ

Primary citation

Structural basis and biased signaling of proton sensation by GPCRs mediated by extracellular histidine rearrangement. Guo, L., Zhu, K., Zhong, Y.N. et al. Mol Cell (2025) 85:1658-1673.e7. DOI 10.1016/j.molcel.2025.03.018 · PubMed

Other PDB entries of the same protein (UniProt P62873 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8QEH 1.43 Å, Crystal structure of the G11 protein heterotrimer bound to FR900359 inhibitor
8QEG 1.7 Å, Crystal structure of the G11 protein heterotrimer bound to YM-254890 inhibitor
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
9YDQ 1.94 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE and allosteric…
9YDP 1.95 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE
6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
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

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