7SQO: Orexin-2 receptor(OX2R)

Structure of the orexin-2 receptor(OX2R) bound to TAK-925, Gi and scFv16. Determined by electron microscopy at 3.17 Å resolution. Released 25 May 2022.

Method: Electron microscopy
Resolution: 3.17 Å
Organisms: Homo sapiens, Bos taurus, synthetic construct
Chains: 5
Atoms: 8,618
Mol. weight: 165.74 kDa
Ligands: A6F, OLA
Released: 25 May 2022

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

Secondary structure: helices and β-sheets

7SQO 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: 9 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	9-31	23
β-strand	33-38	6	2
α-helix	46-54	9
β-strand	185-186	2	2
β-strand	189-191	3	2
β-strand	194-200	7	2
α-helix	208-212	5
α-helix	213-215	3
β-strand	220-226	7	2
α-helix	242-254	13
α-helix	257-259	3
β-strand	263-269	7	2
α-helix	271-280	10
α-helix	296-309	14
β-strand	320-322	3	2
α-helix	331-350	20

Chain B: 3 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-34	5
α-helix	38-39	2
β-strand	47-51	5	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	88-94	7	4
β-strand	104-105	2	5
β-strand	111-114	4	5
β-strand	121-125	5	5
β-strand	134-139	6	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	165-170	6	6
β-strand	175-181	7	6
β-strand	187-191	5	7
β-strand	200-203	4	7
β-strand	207-210	4	7
β-strand	220-222	3	7
β-strand	232-234	3	8
β-strand	240-243	4	8
β-strand	250-254	5	8
β-strand	259-264	6	8
β-strand	273-278	6	9
β-strand	285-289	5	9
β-strand	293-294	2	9
β-strand	295-296	2	10
β-strand	306-307	2	10
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain E: 3 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	12	1	12
α-helix	13	1
β-strand	17-25	9	11
β-strand	33-39	7	13
β-strand	45-51	7	13
α-helix	53-55	3
β-strand	58-60	3	13
β-strand	68-73	6	11
β-strand	78-84	7	11
α-helix	88-90	3
β-strand	93-99	7	13
β-strand	111	1	13
β-strand	115	1	13
β-strand	119	1	12
β-strand	129-130	2	14
β-strand	134-136	3	15
β-strand	143-148	6	14
β-strand	154	1	16
β-strand	160	1	16
β-strand	162-167	6	15
β-strand	174-177	4	15
β-strand	191-196	6	14
β-strand	199-204	6	14
β-strand	214-219	6	15
β-strand	227	1	15
β-strand	231-234	4	15

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
α-helix	45-47	3
α-helix	56-58	3

Chain R: 13 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	56-81	26
α-helix	88-116	29
α-helix	124-156	33
α-helix	166-183	18
α-helix	186-189	4
β-strand	191-192	2	1
β-strand	211-212	2	1
α-helix	218-228	11
α-helix	229-233	5
α-helix	234-252	19
α-helix	294-316	23
α-helix	318-327	10
α-helix	340-361	22
α-helix	362-366	5
α-helix	369-377	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Orexin receptor type 2	R	protein	444	Homo sapiens	O43614 (AlphaFold model)
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	354	Bos taurus	P62871 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	68	Bos taurus	P63212 (AlphaFold model)
scFv-16	E	protein	247	synthetic construct

Sequence of entity 1 (R), FASTA

>7SQO_1 Orexin receptor type 2 (chains R)
MSGTKLEDSPPCRNWSSASELNETQEPFLNPTDYDDEEFLRYLWREYLHPKEYEWVLIAG
YIIVFVVALIGNVLVCVAVWKNHHMRTVTNYFIVNLSLADVLVTITCLPATLVVDITETW
FFGQSLCKVIPYLQTVSVSVSVLTLSCIALDRWYAICHPLMFKSTAKRARNSIVIIWIVS
CIIMIPQAIVMECSTVFPGLANKTTLFTVCDERWGGEIYPKMYHICFFLVTYMAPLCLMV
LAYLQIFRKLWCRQIPGTSSVVQRKWKPLQPVSQPRGPGQPTKSRMSAVAAEIKQIRARR
KTARMLMVVLLVFAICYLPISILNVLKRVFGMFAHTEDRETVYAWFTFSHWLVYANSAAN
PIIYNFLSGKFREEFKAAFSCCCLGVHHRQEDRLTRGRTSTESRKSLTTQISNFDNISKL
SEQVVLTSISTLPAANGAGPLQNW

Sequence of entity 2 (A), FASTA

>7SQO_2 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRDERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 3 (B), FASTA

>7SQO_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHHHMGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMR
TRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYA
PSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTC
ALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHE
SDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLL
AGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (G), FASTA

>7SQO_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFC

Sequence of entity 5 (E), FASTA

>7SQO_5 scFv-16 (chains E)
VQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYA
DTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSA
GGGGSGGGGSGGGGSADIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLEL

Ligands and cofactors

ID	Name	Formula	Copies
A6F	methyl (2R,3S)-3-[(methanesulfonyl)amino]-2-({[(1s,4S)-4-phenylcyclohexyl]oxy}m…	C21 H32 N2 O5 S	1
OLA	Oleic acid	C18 H34 O2	4

Primary citation

Molecular mechanism of the wake-promoting agent TAK-925. Yin, J., Kang, Y., McGrath, A.P. et al. Nat Commun (2022) 13:2902-2902. DOI 10.1038/s41467-022-30601-3 · PubMed

Other PDB entries of the same protein (UniProt O43614 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5WQC 1.96 Å, Crystal structure of human orexin 2 receptor bound to the selective antagonist EMPA…
5WS3 2.3 Å, Crystal structures of human orexin 2 receptor bound to the selective antagonist EMPA…
4S0V 2.5 Å, Crystal structure of the human OX2 orexin receptor bound to the insomnia drug Suvorexant
6TPN 2.61 Å, Crystal structure of the Orexin-2 receptor in complex with HTL6641 at 2.61 A resolution
6TPJ 2.74 Å, Crystal structure of the Orexin-2 receptor in complex with suvorexant at 2.76 A resolution
6TPG 2.74 Å, Crystal structure of the Orexin-2 receptor in complex with EMPA at 2.74 A resolution
7XRR 2.89 Å, Crystal structure of the human OX2R bound to the insomnia drug lemborexant.
7L1V 3.0 Å, Orexin Receptor 2 (OX2R) in Complex with G Protein and Small-Molecule Agonist Compound 1
7L1U 3.2 Å, Orexin Receptor 2 (OX2R) in Complex with G Protein and Natural Peptide-Agonist Orexin B…
21CI 3.29 Å, Crystal structure of human orexin type 2 receptor in complex with vornorexant
7SR8 3.3 Å, Molecular mechanism of the the wake-promoting agent TAK-925

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