7T2G: Mu-opioid receptor - Gi protein complex

CryoEM structure of mu-opioid receptor - Gi protein complex bound to mitragynine pseudoindoxyl (MP). Determined by electron microscopy at 2.5 Å resolution. Released 7 Dec 2022.

Method: Electron microscopy
Resolution: 2.5 Å
Organisms: Homo sapiens, Escherichia coli, Mus musculus
Chains: 4
Atoms: 6,922
Mol. weight: 142.26 kDa
Ligands: EIG, CLR
Released: 7 Dec 2022

Explore 7T2G in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7T2G contains 32 α-helices and 36 β-strands across 4 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, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-32	26
β-strand	34-39	6	1
α-helix	46-52	7
β-strand	185-191	7	1
β-strand	194-200	7	1
α-helix	208-211	4
α-helix	212-215	4
β-strand	220-226	7	1
α-helix	227-231	5
α-helix	242-254	13
β-strand	263-269	7	1
α-helix	271-278	8
α-helix	283-285	3
α-helix	296-309	14
β-strand	319-323	5	1
α-helix	331-351	21

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	6-25	20
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	2
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	89-94	6	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	120-125	6	4
β-strand	134-140	7	4
β-strand	146-151	6	5
β-strand	156-161	6	5
β-strand	166-170	5	5
β-strand	175-180	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	217-223	7	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	259-264	6	7
α-helix	272	1
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	303-308	6	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain C: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-45	16
α-helix	53-55	3

Chain R: 15 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	66-95	30
α-helix	102-119	18
α-helix	121-129	9
α-helix	136-170	35
α-helix	172-178	7
α-helix	181-194	14
α-helix	196-205	10
β-strand	208-211	4	9
β-strand	214-217	4	9
α-helix	222	1
α-helix	225-237	13
α-helix	238-242	5
α-helix	243-259	17
α-helix	269-305	37
α-helix	312-333	22
α-helix	334-338	5
α-helix	341-347	7

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	344	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	C	protein	71	Homo sapiens	P59768 (AlphaFold model)
Soluble cytochrome b562,Mu-type opioid receptor	R	protein	488	Escherichia coli, Mus musculus	P0ABE7 (AlphaFold model), P42866

Sequence of entity 1 (A), FASTA

>7T2G_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>7T2G_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
PGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLA
KIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGG
LDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQ
TTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFP
NGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNV
WDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (C), FASTA

>7T2G_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (R), FASTA

>7T2G_4 Soluble cytochrome b562,Mu-type opioid receptor (chains R)
CLVFADYKDDDDALEVLFQGPADLEDNWETLNDNLKVIEKADNAAQVKDALTKMRAAALD
AQKATPPKLEDKSPDSPEMKDFRHGFDILVGQIDDALKLANEGKVKEAQAAAEQLKTTRN
AYIQKYLAGSPGARSASSLALAIAITALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIY
IFNLALADALATSTLPFQSVNYLMGTWPFGNILCKIVISIDYYNMFTSIFTLCTMSVDRY
IAVCHPVKALDFRTPRNAKIVNVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTW
YWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVV
AVFIVCWTPIHIYVIIKALITIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRC
FREFCIPTSSTILEVLFQGPEQQNSARIRQNTREHPSTANTVDRTNHQLENLEAETAPLP
DIHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
EIG	Mitragynine pseudoindoxyl	C23 H30 N2 O5	1
CLR	Cholesterol	C27 H46 O	2

Primary citation

Insights into distinct signaling profiles of the mu OR activated by diverse agonists. Qu, Q., Huang, W., Aydin, D. et al. Nat Chem Biol (2022). DOI 10.1038/s41589-022-01208-y · 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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