7EW7: SEW2871-bound Sphingosine-1-phosphate receptor 1

Cryo-EM structure of SEW2871-bound Sphingosine-1-phosphate receptor 1 in complex with Gi protein. Determined by electron microscopy at 3.27 Å resolution. Released 29 Sept 2021.

Method: Electron microscopy
Resolution: 3.27 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 9,004
Mol. weight: 176.77 kDa
Ligands: JEX
Released: 29 Sept 2021

Explore 7EW7 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7EW7 contains 29 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 A: 9 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	9-27	19
β-strand	34-40	7	1
α-helix	46-52	7
β-strand	185-190	6	1
β-strand	195-200	6	1
α-helix	210-215	6
β-strand	220-225	6	1
β-strand	233	1	2
α-helix	234	1
β-strand	241	1	2
α-helix	242-254	13
β-strand	263-268	6	1
α-helix	272-280	9
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	1
α-helix	328-350	23

Chain B: 3 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	2-24	23
α-helix	30-33	4
β-strand	47-52	6	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78	1	5
β-strand	81-83	3	4
β-strand	89-91	3	4
β-strand	94	1	5
β-strand	111-114	4	6
β-strand	121-125	5	6
β-strand	134-139	6	6
α-helix	145	1
β-strand	146-151	6	7
β-strand	157-161	5	7
β-strand	165-168	4	7
β-strand	178-181	4	7
β-strand	190-192	3	8
β-strand	198-202	5	8
β-strand	208-212	5	8
β-strand	218-222	5	8
β-strand	232-234	3	9
β-strand	240-243	4	9
β-strand	250-254	5	9
β-strand	262-264	3	9
β-strand	273-277	5	10
β-strand	284	1	11
β-strand	286-289	4	10
β-strand	294-295	2	10
β-strand	298	1	11
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	335-339	5	3

Chain C: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	8-22	15
α-helix	30-43	14
α-helix	44-47	4

Chain D: 13 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	23-32	10
α-helix	47-72	26
α-helix	80-104	25
α-helix	107-110	4
α-helix	114-147	34
α-helix	157-180	24
β-strand	191	1	12
β-strand	199	1	12
α-helix	200-234	35
α-helix	249-268	20
α-helix	270-281	12
α-helix	283	1
α-helix	289-291	3
α-helix	298-312	15
α-helix	316-324	9

Chain E: 1 helix, 23 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	13
β-strand	11-12	2	14
β-strand	19-24	6	13
α-helix	29-31	3
β-strand	33-39	7	15
β-strand	45-51	7	15
β-strand	58-60	3	15
β-strand	68-71	4	13
β-strand	78-83	6	13
β-strand	93-95	3	15
β-strand	98-99	2	15
β-strand	115	1	15
β-strand	118-119	2	14
β-strand	141-142	2	16
β-strand	146-148	3	17
β-strand	155-160	6	16
β-strand	174-179	6	17
β-strand	186-189	4	17
β-strand	195	1	17
β-strand	203-207	5	16
β-strand	211-216	6	16
β-strand	226-231	6	17
β-strand	238-239	2	17
β-strand	243-246	4	17

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	356	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)
Sphingosine 1-phosphate receptor 1	D	protein	531	Homo sapiens	D9IEF7, P21453
scFv16	E	protein	266	Mus musculus

Sequence of entity 1 (A), FASTA

>7EW7_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>7EW7_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQ
MRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCA
YAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDT
TCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTG
HESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRL
LLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (C), FASTA

>7EW7_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (D), FASTA

>7EW7_4 Sphingosine 1-phosphate receptor 1 (chains D)
MKTIIALSYIFCLVFADYKDDDDANIFEMLRIDEGLRLKIYKNTEGYYTIGIGHLLTKSP
SLNAAKSELDKAIGRNTNGVITKDEAEKLFNQDVDAAVRGILRNAKLKPVYDSLDAVRRA
ALINMVFQMGETGVAGFTNSLRMLQQKRWDEAAVNLAKSRWYNQTPNRAKRVITTFRTGT
WDAYMGPTSVPLVKAHRSSVSDYVNYDIIVRHYNYTGKLNISADKENSIKLTSVVFILIC
CFIILENIFVLLTIWKTKKFHRPMYYFIGNLALSDLLAGVAYTANLLLSGATTYKLTPAQ
WFLREGSMFVALSASVFSLLAIAIERYITMLKMKLHNGSNNFRLFLLISACWVISLILGG
LPIMGWNCISALSSCSTVLPLYHKHYILFCTTVFTLLLLSIVILYCRIYSLVRTRSRRLT
FRKNISKASRSSEKSLALLKTVIIVLSVFIACWAPLFILLLLDVGCKVKTCDILFRAEYF
LVLAVLNSGTNPIIYTLTNKEMRRAFIRIMSCCKCPSGDSAHHHHHHHHHH

Sequence of entity 5 (E), FASTA

>7EW7_5 scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAAENLYFQGHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
JEX	5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-3-[3-(trifluoromethyl)phenyl]-1,2…	C20 H10 F6 N2 O S	1

Primary citation

Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition. Yuan, Y., Jia, G., Wu, C. et al. Cell Res (2021) 31:1263-1274. DOI 10.1038/s41422-021-00566-x · PubMed

Other PDB entries of the same protein (UniProt P63096 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
3UMR 2.04 Å, Crystal structure of the G202D mutant of human G-alpha-i1
9P7Z 2.1 Å, NTSR1-Gi-NTS(8-13) Complex in the Canonical, AHD Open State (C-Open-Apo)
2OM2 2.2 Å, Crystal Structure Of Human G[alpha]i1 Bound To The Goloco Motif Of Rgs14
8YN9 2.3 Å, Cryo-EM structure of histamine H4 receptor in complex with histamine and Gi
9HYI 2.3 Å, DP81-bound serotonin 5-HT1A receptor - Gi Protein Complex
9O36 2.3 Å, CryoEM structure of mu-opioid receptor - Gi protein complex bound to fluornitrazene (FNZ)
9P80 2.3 Å, NTSR1-Gi-NTS(8-13) Complex in the Non-Canonical, AHD Open State (NC-Open-Apo)
8XXV 2.33 Å, Cryo-EM Structure of the Prostaglandin D2 Receptor 2-indomethacin Coupled to G Protein
3UMS 2.34 Å, Crystal structure of the G202A mutant of human G-alpha-i1
3ONW 2.38 Å, Structure of a G-alpha-i1 mutant with enhanced affinity for the RGS14 GoLoco motif.
20ZG 2.4 Å, Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the…

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