8Y45: Opioid receptor with biased agonist

Cryo-EM structure of opioid receptor with biased agonist. Determined by electron microscopy at 3.45 Å resolution. Released 27 Nov 2024.

Method: Electron microscopy
Resolution: 3.45 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,867
Mol. weight: 152.92 kDa
Ligands: A1LXY
Released: 27 Nov 2024

Explore 8Y45 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8Y45 contains 29 α-helices and 69 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, 4 β-strands

Element	Residues	Length	Sheet
α-helix	46-76	31
α-helix	83-111	29
α-helix	119-151	33
α-helix	154-156	3
α-helix	162-185	24
β-strand	187	1	1
β-strand	190-192	3	2
β-strand	195-197	3	2
β-strand	200	1	1
α-helix	212-218	7
α-helix	219-223	5
α-helix	224-242	19
α-helix	250-286	37
α-helix	296-317	22
α-helix	323-329	7

Chain B: 3 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	2-25	24
α-helix	32-34	3
α-helix	38-42	5
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	103-105	3	5
β-strand	111-114	4	5
β-strand	120	1	6
β-strand	122-125	4	5
β-strand	134-137	4	5
β-strand	140	1	6
β-strand	148-151	4	7
β-strand	158-161	4	7
β-strand	166-168	3	7
β-strand	177-180	4	7
β-strand	190	1	8
β-strand	198-201	4	8
β-strand	207-212	6	8
β-strand	217-223	7	8
β-strand	232-234	3	9
β-strand	240-243	4	9
β-strand	250-254	5	9
β-strand	260-264	5	9
β-strand	273-276	4	10
β-strand	286-289	4	10
β-strand	294-297	4	10
β-strand	304-307	4	10
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain C: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-43	14
α-helix	53-55	3

Chain D: 10 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	9-29	21
β-strand	34-37	4	11
α-helix	46-49	4
α-helix	50-52	3
β-strand	185-191	7	11
β-strand	196-202	7	11
α-helix	209-211	3
α-helix	213-215	3
β-strand	221-222	2	11
β-strand	224-227	4	12
α-helix	243-255	13
β-strand	264	1	11
β-strand	265	1	13
β-strand	267-270	4	12
α-helix	272-275	4
α-helix	284-286	3
α-helix	297-309	13
β-strand	320	1	13
β-strand	323-324	2	12
α-helix	333-350	18

Chain S: 2 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	14
β-strand	11-12	2	15
β-strand	18-25	8	14
α-helix	29-31	3
β-strand	33-39	7	16
β-strand	45-50	6	16
β-strand	59-60	2	16
β-strand	68	1	14
β-strand	71-73	3	14
β-strand	78-83	6	14
β-strand	93-99	7	16
β-strand	111	1	16
β-strand	115-116	2	16
β-strand	118-119	2	15
β-strand	140-141	2	17
β-strand	146	1	18
β-strand	155-159	5	19
β-strand	160-161	2	17
β-strand	174-179	6	20
β-strand	186-187	2	20
β-strand	203-208	6	19
β-strand	211-216	6	19
α-helix	221-223	3
β-strand	225	1	21
β-strand	226-231	6	20
β-strand	244	1	18
β-strand	245	1	21

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Delta-type opioid receptor	A	protein	325	Homo sapiens	P41143 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	358	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-2	D	protein	355	Homo sapiens	P04899 (AlphaFold model)
scFv16	S	protein	266	Mus musculus
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	C	protein	71	Homo sapiens	P59768 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8Y45_1 Delta-type opioid receptor (chains A)
DYKDDDDAGPPGARSASSLALAIAITALYSAVCAVGLLGNVLVMFGIVRYTKMKTATNIY
IFNLALADALATSTLPFQSAKYLMETWPFGELLCKAVLSIDYYNMFTSIFTLTMMSVDRY
IAVCHPVKALDFRTPAKAKLINICIWVLASGVGVPIMVMAVTRPRDGAVVCMLQFPSPSW
YWDTVTKICVFLFAFVVPILIITVCYGLMLLRLRSVRLLSGSKEKDRSLRRITRMVLVVV
GAFVVCWAPIHIFVIVWTLVDIDRRDPLVVAALHLCIALGYANSSLNPVLYAFLDENFKR
CFRQLCRKPCGRPDPSSFSRAREAT

Sequence of entity 2 (B), FASTA

>8Y45_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MPPHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (D), FASTA

>8Y45_3 Guanine nucleotide-binding protein G(i) subunit alpha-2 (chains D)
MGCTLSAEDKAAAERSKMIDKNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEDG
YSEEECRQYRAVVYSNTIQSIMAIVKAMGNLQIDFADPSRADDARQLFALSCTAEEQGVL
PDDLSGVIRRLWADHGVQACFGRSREYQLNDSAAYYLNDLERIAQSDYIPTQQDVLRTRV
KTTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSAYDLVLAEDEE
MNRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKITHSPLTICFPEYTGANKYDEA
ASYIQSKFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 4 (S), FASTA

>8Y45_4 scFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAAENLYFQGHHHHHHHH

Sequence of entity 5 (C), FASTA

>8Y45_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Ligands and cofactors

ID	Name	Formula	Copies
A1LXY	~{N},~{N}-diethyl-4-(5-oxidanylspiro[chromene-2,4'-piperidine]-4-yl)benzamide	C24 H28 N2 O3	1

Primary citation

Cryo-EM structure of small-molecule agonist bound delta opioid receptor-G i complex enables discovery of biased compound. Cheng, L., Miao, Z., Liu, S. et al. Nat Commun (2024) 15:8284-8284. DOI 10.1038/s41467-024-52601-1 · PubMed

Other PDB entries of the same protein (UniProt P41143 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4N6H 1.8 Å, 1.8 A Structure of the human delta opioid 7TM receptor (PSI Community Target)
9YDP 1.95 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE
9CGK 2.62 Å, CryoEM structure of delta opioid receptor bound to G proteins and a full bitopic agonist
4RWD 2.7 Å, XFEL structure of the human delta opioid receptor in complex with a bifunctional peptide
9XDQ 2.79 Å, Cryo-EM structure of BMS986187 bound DOR-Gi complex
6PT2 2.8 Å, Crystal structure of the active delta opioid receptor in complex with the peptide…
9CGJ 2.8 Å, CryoEM structure of delta opioid receptor bound to G proteins and a partial agonist
8Y71 2.97 Å, positive allosteric modulator(BMS986187)-bound delta-opioid receptor-Gi complex
8F7S 3.0 Å, Gi bound delta-opioid receptor in complex with deltorphin
9PPX 3.04 Å, CryoEM structure of delta opioid receptor bound to G proteins and naltrexone
9XF4 3.05 Å, Cryo-EM structure of Leu-enkephalin-BMS-986187-bound DOR-Gi2 complex
9PPY 3.1 Å, CryoEM structure of delta opioid receptor bound to G proteins and met-enkephalin

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