9W49: PDB entry 9W49

Cryo-EM structure of human kappa opioid receptor -G protein signaling complex bound with U-50488H. Determined by electron microscopy at 2.9 Å resolution. Released 19 Nov 2025.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,284
Mol. weight: 149.35 kDa
Ligands: A1LWX
Released: 19 Nov 2025

Explore 9W49 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9W49 contains 32 α-helices and 66 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: 11 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-29	23
α-helix	30-32	3
β-strand	33-40	8	1
α-helix	47-52	6
β-strand	185-190	6	1
β-strand	195-200	6	1
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	1
β-strand	233	1	2
β-strand	241	1	2
α-helix	242-254	13
α-helix	257-259	3
β-strand	263-269	7	1
α-helix	271-280	10
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	1
α-helix	331-351	21

Chain B: 4 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	6-25	20
α-helix	30-34	5
α-helix	38-40	3
β-strand	47-52	6	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
α-helix	95	1
β-strand	100-105	6	5
β-strand	111-116	6	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	175-180	6	6
β-strand	187	1	7
β-strand	191-192	2	8
β-strand	198-202	5	8
β-strand	203	1	7
β-strand	207-212	6	8
β-strand	218-223	6	8
β-strand	229-234	6	9
β-strand	240-245	6	9
β-strand	250-254	5	9
β-strand	260-264	5	9
β-strand	273-278	6	10
β-strand	284-289	6	10
β-strand	294-298	5	10
β-strand	303-308	6	10
β-strand	318-320	3	3
β-strand	327-329	3	3
β-strand	335-339	5	3

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	12-23	12
α-helix	30-43	14
α-helix	53-55	3

Chain R: 12 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	59-82	24
α-helix	83-87	5
α-helix	92-121	30
α-helix	127-161	35
α-helix	163-169	7
α-helix	172-196	25
β-strand	199	1	11
β-strand	210	1	11
α-helix	222-231	10
α-helix	232-236	5
α-helix	237-255	19
α-helix	263-298	36
α-helix	310-332	23
α-helix	335-340	6

Chain S: 2 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	12
β-strand	10-12	3	13
β-strand	17-25	9	12
α-helix	29-31	3
β-strand	33-39	7	13
β-strand	45-51	7	13
β-strand	58-60	3	13
β-strand	68-73	6	12
β-strand	78-84	7	12
β-strand	92-99	8	13
β-strand	110-111	2	13
β-strand	115-119	5	13
α-helix	125-127	3
β-strand	128-129	2	14
β-strand	135-136	2	15
β-strand	143-149	7	14
β-strand	154	1	16
β-strand	160	1	16
β-strand	162-167	6	17
β-strand	174-179	6	17
β-strand	182-183	2	17
β-strand	191-196	6	14
β-strand	199-204	6	14
β-strand	214-219	6	17
β-strand	227	1	17
β-strand	228	1	14
β-strand	232	1	17
β-strand	233-234	2	15

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	345	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
Kappa-type opioid receptor	R	protein	314	Homo sapiens	P41145 (AlphaFold model)
scFv16	S	protein	255	Mus musculus

Sequence of entity 1 (A), FASTA

>9W49_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>9W49_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
GPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>9W49_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (R), FASTA

>9W49_4 Kappa-type opioid receptor (chains R)
LGSISPAIPVIITAVYSVVFVVGLVGNSLVMFVIIRYTKMKTATNIYIFNLALADALVTT
TMPFQSTVYLMNSWPFGDVLCKIVLSIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFR
TPLKAKIINICIWLLSSSVGISAIVLGGTKVREDVDVIECSLQFPDDDYSWWDLFMKICV
FIFAFVIPVLIIIVCYTLMILRLKSVRLLSGSREKDRNLRRITRLVLVVVAVFVVCWTPI
HIFILVEALGSTSHSTAALSSYYFCIALGYTNSSLNPILYAFLDENFKRCFRDFCFPLKM
RMERQSTSLEVLFQ

Sequence of entity 5 (S), FASTA

>9W49_5 scFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGENLYFQ

Ligands and cofactors

ID	Name	Formula	Copies
A1LWX	2-(3,4-dichlorophenyl)-~{N}-methyl-~{N}-[(1~{R},2~{R})-2-pyrrolidin-1-ylcyclohe…	C19 H26 Cl2 N2 O	1

Primary citation

Structural and dynamic insights into the biased signaling mechanism of the human kappa opioid receptor. Suno-Ikeda, C., Nishikawa, R., Suzuki, R. et al. Nat Commun (2025) 16:9392-9392. DOI 10.1038/s41467-025-64882-1 · 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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