8EF6: Morphine-bound mu-opioid receptor-Gi complex

Morphine-bound mu-opioid receptor-Gi complex. Determined by electron microscopy at 3.2 Å resolution. Released 9 Nov 2022.

Method: Electron microscopy
Resolution: 3.2 Å
Organisms: Homo sapiens, Rattus norvegicus, Bos taurus
Chains: 7
Atoms: 11,686
Mol. weight: 240.46 kDa
Ligands: MOI, CLR
Released: 9 Nov 2022

Explore 8EF6 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8EF6 contains 54 α-helices and 66 β-strands across 7 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: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-32	26
β-strand	34-40	7	2
α-helix	42-44	3
α-helix	46-54	9
β-strand	185-190	6	2
β-strand	195-200	6	2
α-helix	208-210	3
α-helix	212-216	5
β-strand	220-226	7	2
α-helix	227-229	3
β-strand	233	1	3
β-strand	241	1	3
α-helix	242-254	13
β-strand	263-269	7	2
α-helix	271-280	10
α-helix	296-309	14
β-strand	319-323	5	2
α-helix	328-351	24

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	7-25	19
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	4
β-strand	58-63	6	5
β-strand	69-74	6	5
β-strand	78-83	6	5
β-strand	89-94	6	5
β-strand	100-105	6	6
β-strand	111-116	6	6
β-strand	121-125	5	6
β-strand	135-139	5	6
β-strand	148-151	4	7
β-strand	156-160	5	7
β-strand	166-170	5	7
β-strand	176-180	5	7
β-strand	187-192	6	8
β-strand	198-203	6	8
β-strand	208-212	5	8
β-strand	218-222	5	8
β-strand	229-234	6	9
β-strand	240-245	6	9
β-strand	250-254	5	9
β-strand	259-264	6	9
α-helix	272	1
β-strand	273-278	6	10
β-strand	284-289	6	10
β-strand	294-298	5	10
β-strand	304-308	5	10
β-strand	315-320	6	4
β-strand	327-331	5	4
β-strand	336-339	4	4

Chain C: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	11-23	13
α-helix	30-43	14
α-helix	53-55	3

Chain E: 6 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	10-12	3	12
β-strand	17-25	9	11
α-helix	29-31	3
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	110-111	2	13
β-strand	115-116	2	13
β-strand	117-119	3	12
α-helix	139-141	3
β-strand	142-143	2	14
β-strand	147-149	3	15
β-strand	152	1	16
β-strand	154	1	16
β-strand	156-161	6	14
β-strand	167	1	17
β-strand	173	1	17
β-strand	175-180	6	15
β-strand	186-191	6	15
β-strand	195-196	2	15
α-helix	197	1
β-strand	204-209	6	14
β-strand	212-217	6	14
β-strand	227-232	6	15
α-helix	238	1
β-strand	244-247	4	15

Chain F: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	337-351	15

Chains M and R: 15 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	67-94	28
α-helix	95-99	5
α-helix	104-121	18
α-helix	123-132	10
α-helix	139-172	34
α-helix	174-180	7
α-helix	183-207	25
β-strand	208-213	6	18
β-strand	216-221	6	18
α-helix	224	1
α-helix	227-239	13
α-helix	240-244	5
α-helix	245-263	19
α-helix	271-307	37
α-helix	314-335	22
α-helix	336-340	5
α-helix	343-351	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Mu-type opioid receptor	M, R	protein	367	Homo sapiens	P35372 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	A, F	protein	354	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	353	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	C	protein	68	Bos taurus	P63212 (AlphaFold model)
scFV16	E	protein	248	synthetic construct

Sequence of entity 1 (M, R), FASTA

>8EF6_1 Mu-type opioid receptor (chains M, R)
DSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCPP
TGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALATS
TLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDFR
TPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFIF
AFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHIY
VIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNIE
QQNSTRI

Sequence of entity 2 (A, F), FASTA

>8EF6_2 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A, F)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 3 (B), FASTA

>8EF6_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRT
RRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAP
SGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCA
LWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHES
DINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLA
GYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (C), FASTA

>8EF6_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFC

Sequence of entity 5 (E), FASTA

>8EF6_5 scFV16 (chains E)
MVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
AGGGGSGGGGSGGGGSADIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQ
RPGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTF
GAGTKLEL

Ligands and cofactors

ID	Name	Formula	Copies
MOI	(7R,7AS,12BS)-3-methyl-2,3,4,4A,7,7A-hexahydro-1H-4,12-METHANO[1]BENZOFURO[3,2-…	C17 H19 N O3	2
CLR	Cholesterol	C27 H46 O	10

Primary citation

Molecular recognition of morphine and fentanyl by the human mu-opioid receptor. Zhuang, Y., Wang, Y., He, B. et al. Cell (2022) 185:4361-4375.e19. DOI 10.1016/j.cell.2022.09.041 · PubMed

Other PDB entries of the same protein (UniProt P35372 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8Y72 2.65 Å, positive allosteric modulator(BMS986122)-bound mu-opioid receptor-Gi complex
9PY4 2.78 Å, Primed-state loperamide-mu opioid receptor-Gi GDPbS complex (rebound)
8EFO 2.8 Å, PZM21-bound mu-opioid receptor-Gi complex
9WST 2.8 Å, Cryo-EM structure of DAMGO-muOR-Gz-scFv16 complex
8Y73 2.84 Å, positive allosteric modulator(MPAM-15)-bound mu-opioid receptor-Gi complex
9PA2 2.86 Å, PCP bound mu-opioid receptor in complex with Gi1
9PA5 2.92 Å, (S)-ketamine bound mu-opioid receptor in complex with Gi1
23SO 2.95 Å, Cryo-EM structure of the cebranopadol-mu opioid receptor-Gi complex
9VJT 2.97 Å, Cryo-EM structure of MST-OR complex
8K9K 2.98 Å, Full agonist-bound mu-type opioid receptor-G protein complex
10TM 3.0 Å, Cryo-EM structure of MOR bound with DAMGO
9PUD 3.0 Å, Cryo-EM structure of MOR-Gi1 complex protein bound with DAMGO

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