9JCO: PDB entry 9JCO

Cryo-EM structure of the proton-sensing GPCR (GPR4)-Gs protein complex at pH 6.5. Determined by electron microscopy at 2.36 Å resolution. Released 9 Jul 2025.

Method: Electron microscopy
Resolution: 2.36 Å
Organisms: Homo sapiens, Lama glama
Chains: 5
Atoms: 8,437
Mol. weight: 162.41 kDa
Ligands: A1L35, CLR
Released: 9 Jul 2025

Explore 9JCO in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9JCO contains 36 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: 12 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	33-40	8	1
α-helix	46-53	8
β-strand	184-191	8	1
β-strand	194-201	8	1
α-helix	211-215	5
β-strand	220-226	7	1
α-helix	233-245	13
α-helix	247-249	3
α-helix	252-253	2
β-strand	254-259	6	1
α-helix	261-270	10
α-helix	275-277	3
α-helix	280-282	3
α-helix	293-294	2
α-helix	299-318	20
β-strand	326-330	5	1
α-helix	338-357	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	11-29	19
α-helix	35-38	4
α-helix	39-41	3
α-helix	43-44	2
β-strand	51-57	7	2
β-strand	63-68	6	3
β-strand	74-79	6	3
β-strand	83-88	6	3
β-strand	94-99	6	3
β-strand	105-110	6	4
β-strand	116-121	6	4
β-strand	125-130	6	4
β-strand	139-145	7	4
β-strand	151-156	6	5
β-strand	161-166	6	5
β-strand	171-175	5	5
β-strand	180-185	6	5
β-strand	194-197	4	6
β-strand	203-207	5	6
β-strand	213-217	5	6
β-strand	223-227	5	6
β-strand	234-239	6	7
β-strand	245-250	6	7
β-strand	255-259	5	7
β-strand	264-269	6	7
β-strand	278-283	6	8
β-strand	289-294	6	8
β-strand	299-303	5	8
β-strand	309-312	4	8
β-strand	320-325	6	2
β-strand	332-336	5	2
β-strand	340-345	6	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-42	13
α-helix	45-47	3

Chain N: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11	1	10
β-strand	17-25	9	9
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	9
β-strand	78-84	7	9
α-helix	88-90	3
β-strand	92-98	7	11
β-strand	118	1	11
β-strand	122-124	3	11
β-strand	125	1	10

Chain R: 14 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	19-47	29
α-helix	51-78	28
β-strand	82	1	12
α-helix	87-89	3
α-helix	90-94	5
α-helix	95-120	26
α-helix	131-148	18
α-helix	151-154	4
β-strand	158	1	13
β-strand	166	1	12
β-strand	168	1	13
α-helix	176-184	9
α-helix	185-191	7
α-helix	192-210	19
α-helix	216-253	38
α-helix	258-274	17
α-helix	277-285	9
α-helix	291-305	15

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha	A	protein	361	Homo sapiens	A0A5A9NRD5 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	518	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	70	Homo sapiens	P59768 (AlphaFold model)
Nanobody 35	N	protein	128	Lama glama
G-protein coupled receptor 4	R	protein	362	Homo sapiens	P46093 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>9JCO_1 Guanine nucleotide-binding protein G(s) subunit alpha (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHLRQYEL
L

Sequence of entity 2 (B), FASTA

>9JCO_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGGGGSSG
VFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVI
IPYEGLSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAV
FDGKKITVTGTLWNGNKIIDERLITPDGSMLFRVTINS

Sequence of entity 3 (G), FASTA

>9JCO_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL

Sequence of entity 4 (N), FASTA

>9JCO_4 Nanobody 35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSS

Sequence of entity 5 (R), FASTA

>9JCO_5 G-protein coupled receptor 4 (chains R)
MGNHTWEGCHVDSRVDHLFPPSLYIFVIGVGLPTNCLALWAAYRQVQQRNELGVYLMNLS
IADLLYICTLPLWVDYFLHHDNWIHGPGSCKLFGFIFYTNIYISIAFLCCISVDRYLAVA
HPLRFARLRRVKTAVAVSSVVWATELGANSAPLFHDELFRDRYNHTFCFEKFPMEGWVAW
MNLYRVFVGFLFPWALMLLSYRGILRAVRGSVSTERQEKAKIKRLALSLIAIVLVCFAPY
HVLLLSRSAIYLGRPWDCGFEERVFSAYHSSLAFTSLNCVADPILYCLVNEGARSDVAKA
LHNLLRFLASDKPQEMANASLTLETPLTSKRNSTAKAMTGSWAATPPSQGDQVQLKMLPP
AQ

Ligands and cofactors

ID	Name	Formula	Copies
A1L35	2-[[(2~{R})-3-acetyloxy-2-oxidanyl-propoxy]-oxidanyl-phosphoryl]oxyethyl-trimet…	C10 H23 N O7 P	2
CLR	Cholesterol	C27 H46 O	2

Primary citation

Molecular mechanism of pH sensing and activation in GPR4 reveals proton-mediated GPCR signaling. You, C., Guo, S., Zhang, T. et al. Cell Discov (2025) 11:59-59. DOI 10.1038/s41421-025-00807-y · PubMed

Other PDB entries of the same protein (UniProt A0A5A9NRD5 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9X3Z 2.54 Å, NPFF bound Mas1 Receptor Complex
27XK 2.64 Å, A cryo-EM structure of GLP1-Y11-GLP1R-Gs complex
9UWM 3.1 Å, A combined cryo_EM structure of Cagrilintide-CTR-Gs complex
9UWQ 3.1 Å, A combined Cryo_EM structure of Cagrilintide-AMY1R-Gs complex

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