8QOT: Mu opioid receptor

Structure of the mu opioid receptor bound to the antagonist nanobody NbE. Determined by electron microscopy at 3.2 Å resolution. Released 27 Dec 2023.

Method: Electron microscopy
Resolution: 3.2 Å
Organisms: Mus musculus, Lama glama, synthetic construct
Chains: 5
Atoms: 7,493
Mol. weight: 143.88 kDa
Released: 27 Dec 2023

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

Secondary structure: helices and β-sheets

8QOT contains 25 α-helices and 72 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, 2 β-strands

Element	Residues	Length	Sheet
α-helix	67-94	28
α-helix	102-130	29
α-helix	137-169	33
α-helix	173-176	4
α-helix	181-204	24
β-strand	206-210	5	1
β-strand	215-219	5	1
α-helix	225-257	33
α-helix	261-265	5
α-helix	272-305	34
α-helix	308-310	3
α-helix	312-338	27
α-helix	342-349	8

Chain B: 0 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	5-9	5	2
β-strand	12-14	3	3
β-strand	20-27	8	2
β-strand	35-41	7	3
β-strand	48-54	7	3
β-strand	59-61	3	3
β-strand	69-74	6	2
β-strand	79-84	6	2
β-strand	93-105	13	3
β-strand	108-114	7	3
β-strand	119-123	5	3

Chain H: 7 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	4
β-strand	11-12	2	5
β-strand	18-25	8	4
α-helix	29-31	3
β-strand	33-39	7	6
β-strand	45-51	7	6
β-strand	57-59	3	6
β-strand	67-72	6	4
β-strand	77-82	6	4
α-helix	84-86	3
β-strand	88-91	4	6
β-strand	93	1	7
β-strand	94-95	2	6
α-helix	99-100B	4
β-strand	100D	1	8
β-strand	100G	1	8
β-strand	103	1	7
β-strand	107-109	3	6
β-strand	110-111	2	5
β-strand	117	1	9
β-strand	120-124	5	10
α-helix	125-127	3
β-strand	135-145	11	10
β-strand	146	1	9
β-strand	151-154	4	11
α-helix	155-157	3
β-strand	164-165	2	10
α-helix	166-168	3
β-strand	169-170	2	10
β-strand	176-185	10	10
α-helix	186-188	3
β-strand	194-200	7	11
β-strand	205-211	7	11

Chain K: 1 helix, 10 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	19
β-strand	19-25	7	19
β-strand	34-39	6	20
β-strand	46-51	6	20
β-strand	57-59	3	20
β-strand	67-72	6	19
β-strand	77-82	6	19
α-helix	84-86	3
β-strand	89-95	7	20
β-strand	100D-103	4	20
β-strand	107-108	2	20

Chain L: 6 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	5	1	12
β-strand	11-13	3	13
β-strand	19-23	5	14
β-strand	24	1	12
α-helix	31-32	2
β-strand	33-38	6	15
β-strand	45-48	4	15
β-strand	54	1	15
β-strand	62-67	6	14
β-strand	70-75	6	14
α-helix	80-82	3
β-strand	85-92	8	15
β-strand	95-97	3	15
β-strand	102-103	2	15
β-strand	104-106	3	13
β-strand	111	1	16
α-helix	112-113	2
β-strand	114-118	5	17
α-helix	119-121	3
α-helix	122-127	6
β-strand	129-139	11	17
β-strand	140	1	16
β-strand	145-150	6	18
β-strand	153-154	2	18
β-strand	159-163	5	17
β-strand	173-182	10	17
α-helix	183-188	6
β-strand	191-197	7	18
β-strand	205-210	6	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Mu-type opioid receptor	A	protein	482	Mus musculus	P42866 (AlphaFold model)
Nanobody E (NbE)	B	protein	171	Lama glama
NabFab HC	H	protein	262	synthetic construct
NabFab LC	L	protein	238	synthetic construct
Anti-Fab Nanobody	K	protein	159	Lama glama

Sequence of entity 1 (A), FASTA

>8QOT_1 Mu-type opioid receptor (chains A)
MKTIIALSYIFCLVFADYKDDDDAMGPGNISDCSDPLAPASCSPAPGSWLNLSHVDGNQS
DPCGPNRTGLGENLYFQGSHSLCPQTGSPSMVTAITIMALYSIVCVVGLFGNFLVMYVIV
RYTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGNILCKIVISIDYYNMFTS
IFTLCTMSVDRYIAVCHPVKALDFRTPRNAKIVNVCNWILSSAIGLPVMFMATTKYRQGS
IDCTLTFSHPTWYWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRN
LRRITRMVLVVVAVFIVCWTPIHIYVIIKALITIPETTFQTVSWHFCIALGYTNSCLNPV
LYAFLDENFKRCFREFCIPTSSTILEVLFQGPEQQNSARIRQNTREHPSTANTVDRTNHQ
LENLEAETAPLPSSLAEENLYFQSWSHPQFEKGGGSGGGSGGGSWSHPQFEKGAHHHHHH
HH

Sequence of entity 2 (B), FASTA

>8QOT_2 Nanobody E (NbE) (chains B)
VKKLLFAIPLVVPFYAAQPAMAQVQLVESGGGLVQAGGSLRLSCAASGSISSISTMGWYR
QAPGKERELVAAITSGGSTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNFK
YYSGSYFYKSEYDYWGKGTPVTVSSAAAHHHHHHGAAEQKLISEEDLNGAA

Sequence of entity 3 (H), FASTA

>8QOT_3 NabFab HC (chains H)
MKKNIAFLLASMFVFSIATNAYAEISEVQLVESGGGLVQPGGSLRLSCAASGFNFSYYSI
HWVRQAPGKGLEWVAYISSSSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVY
YCARGYQYWQYHASWYWNGGLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHT

Sequence of entity 4 (L), FASTA

>8QOT_4 NabFab LC (chains L)
MKKNIAFLLASMFVFSIATNAYASDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWY
QQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSSSLI
TFGQGTKVEIKRTVAAPSVFIFPPSDSQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Sequence of entity 5 (K), FASTA

>8QOT_5 Anti-Fab Nanobody (chains K)
MKYLLPTAAAGLLLLAAQPAMAMHHHHHHGENLYFQGSQVQLQESGGGLVQPGGSLRLSC
AASGRTISRYAMSWFRQAPGKEREFVAVARRSGDGAFYADSVQGRFTVSRDDAKNTVYLQ
MNSLKPEDTAVYYCAIDSDTFYSGSYDYWGQGTQVTVSS

Primary citation

Structural basis of mu-opioid receptor targeting by a nanobody antagonist. Yu, J., Kumar, A., Zhang, X. et al. Nat Commun (2024) 15:8687-8687. DOI 10.1038/s41467-024-52947-6 · PubMed

Other PDB entries of the same protein (UniProt P42866 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5C1M 2.07 Å, Crystal structure of active mu-opioid receptor bound to the agonist BU72
8E0G 2.1 Å, Re-refined model of active mu-opioid receptor (PDB 5c1m) as an adduct with BU72
9O36 2.3 Å, CryoEM structure of mu-opioid receptor - Gi protein complex bound to fluornitrazene (FNZ)
9ODF 2.4 Å, Structure of the MOR/Gi/Lofentanil Complex, GTP-bound G-Primed
9ODN 2.4 Å, Structure of the MOR/Gi/DAMGO Complex, GTP-Bound, G-Primed
7T2G 2.5 Å, CryoEM structure of mu-opioid receptor - Gi protein complex bound to mitragynine…
9ODE 2.5 Å, Structure of the MOR/Gi/Lofentanil Complex, Nucleotide Free
4DKL 2.8 Å, Crystal structure of the mu-opioid receptor bound to a morphinan antagonist
7UL4 2.8 Å, CryoEM Structure of Inactive MOR Bound to Alvimopan and Mb6
9ODM 2.8 Å, Structure of the MOR/Gi/DAMGO Complex, Nucleotide Free, Baseline
9WSV 2.8 Å, Cryo-EM structure of DAMGO-muOR-arrestin-1-Fab30 complex
9WSW 2.8 Å, Cryo-EM structure of endomorphin-1-muOR-Gz-scFv16 complex

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