9VO0: Gi coupled Sphingosine 1-phosphate receptor

Cryo-EM structure of Gi coupled Sphingosine 1-phosphate receptor bound with Ponesimod. Determined by electron microscopy at 2.79 Å resolution. Released 28 Jan 2026.

Method: Electron microscopy
Resolution: 2.79 Å
Organisms: Homo sapiens, Mus musculus, Escherichia coli
Chains: 5
Atoms: 8,906
Mol. weight: 174.8 kDa
Ligands: A1ESZ
Released: 28 Jan 2026

Explore 9VO0 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9VO0 contains 36 α-helices and 65 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: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-23	21
α-helix	29-32	4
α-helix	37-38	2
β-strand	46-50	5	1
β-strand	57-61	5	2
β-strand	68-73	6	2
β-strand	77-82	6	2
β-strand	87-93	7	2
β-strand	99-104	6	3
β-strand	110-115	6	3
β-strand	120-124	5	3
β-strand	133-138	6	3
β-strand	145-150	6	4
β-strand	155-160	6	4
β-strand	164-169	6	4
β-strand	175-180	6	4
β-strand	186-191	6	5
β-strand	197-202	6	5
β-strand	207-211	5	5
β-strand	217-221	5	5
β-strand	228-233	6	6
β-strand	239-244	6	6
β-strand	249-253	5	6
β-strand	259-263	5	6
α-helix	271	1
β-strand	272-277	6	7
β-strand	283-288	6	7
β-strand	293-297	5	7
β-strand	303-306	4	7
β-strand	314-319	6	1
β-strand	326-330	5	1
β-strand	335-338	4	1

Chain C: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	54-55	2

Chain D: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-40	7	8
α-helix	46-55	10
β-strand	185-191	7	8
β-strand	194-200	7	8
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	8
α-helix	227-230	4
β-strand	233	1	9
β-strand	241	1	9
α-helix	242-254	13
β-strand	263-269	7	8
α-helix	271-277	7
α-helix	283-285	3
α-helix	296-309	14
β-strand	319-323	5	8
α-helix	331-350	20

Chain E: 5 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	11-12	2	11
β-strand	17-25	9	10
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	10
β-strand	78-84	7	10
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	110-111	2	12
β-strand	115-117	3	12
β-strand	118-119	2	11
β-strand	140-141	2	13
β-strand	146-149	4	14
β-strand	154-161	8	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	211-217	7	13
α-helix	221-223	3
β-strand	226-231	6	14
β-strand	239	1	14
β-strand	243-247	5	14

Chain F: 14 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	24-32	9
α-helix	49-72	24
α-helix	74-76	3
α-helix	79-104	26
α-helix	108-111	4
α-helix	114-147	34
α-helix	157-176	20
α-helix	177-180	4
β-strand	183	1	16
α-helix	188-190	3
β-strand	191	1	17
β-strand	198	1	16
β-strand	199	1	17
α-helix	200-233	34
α-helix	250-281	32
α-helix	289-292	4
α-helix	293-313	21
α-helix	316-320	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	A	protein	357	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)
Guanine nucleotide-binding protein G(i) subunit alpha-1	D	protein	354	Homo sapiens	P63096 (AlphaFold model)
scFv16	E	protein	251	Mus musculus
Soluble cytochrome b562,Sphingosine 1-phosphate receptor 1	F	protein	534	Escherichia coli, Homo sapiens	P0ABE7 (AlphaFold model), P21453

Sequence of entity 1 (A), FASTA

>9VO0_1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains A)
HHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRI
QMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTC
AYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGD
TTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFT
GHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGR
LLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 2 (C), FASTA

>9VO0_2 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 3 (D), FASTA

>9VO0_3 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains D)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 4 (E), FASTA

>9VO0_4 scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAA

Sequence of entity 5 (F), FASTA

>9VO0_5 Soluble cytochrome b562,Sphingosine 1-phosphate receptor 1 (chains F)
MKTIIALSYIFCLVFADYKDDDDKLEVLFQGPGSADLEDNWETLNDNLKVIEKADNAAQV
KDALTKMRAAALDAQKATPPKLEDKSPDSPEMKDFRHGFDILVGQIDDALKLANEGKVKE
AQAAAEQLKTTRNAYIQKYLMGPTSVPLVKAHRSSVSDYVNYDIIVRHYNYTGKLNISAD
KENSIKLTSVVFILICCFIILENIFVLLTIWKTKKFHRPMYYFIGNLALSDLLAGVAYTA
NLLLSGATTYKLTPAQWFLREGSMFVALSASVFSLLAIAIERYITMLKMKLHNGSNNFRL
FLLISACWVISLILGGLPIMGWNCISALSSCSTVLPLYHKHYILFCTTVFTLLLLSIVIL
YCRIYSLVRTRSRRLTFRKNISKASRSSEKSLALLKTVIIVLSVFIACWAPLFILLLLDV
GCKVKTCDILFRAEYFLVLAVLNSGTNPIIYTLTNKEMRRAFIRIMSCCKCPSGDSAGKF
KRPIIAGMEFSRSKSDNSSHPQKDEGDNPETIMSSGNVNSSSLEHHHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
A1ESZ	(2~{Z},5~{Z})-5-[[4-[(2~{R})-2,3-bis(oxidanyl)propoxy]-3-chloranyl-phenyl]methy…	C23 H25 Cl N2 O4 S	1

Primary citation

Structural insights into subtype-specific agonist recognition by sphingosine-1-phosphate receptors. Yu, L., Jiao, H., Pang, B. et al. PLoS Biol (2026) 24:e3003381-e3003381. DOI 10.1371/journal.pbio.3003381 · 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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