8GHV: Cannabinoid Receptor 1-G Protein Complex

Cannabinoid Receptor 1-G Protein Complex. Determined by electron microscopy at 2.8 Å resolution. Released 24 May 2023.

Method: Electron microscopy
Resolution: 2.8 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,237
Mol. weight: 169.79 kDa
Ligands: ZI5
Released: 24 May 2023

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

Secondary structure: helices and β-sheets

8GHV contains 26 α-helices and 62 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: 7 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	9-29	21
β-strand	33-39	7	1
α-helix	46-52	7
β-strand	185-191	7	1
β-strand	194-200	7	1
α-helix	213-215	3
β-strand	220-226	7	1
α-helix	242-254	13
β-strand	263-269	7	1
α-helix	271-277	7
α-helix	296-308	13
β-strand	319-323	5	1
α-helix	331-350	20

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
α-helix	30-33	4
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	146-153	8	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	208-212	5	6
β-strand	218-222	5	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
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	304-308	5	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	8-21	14
α-helix	30-43	14
α-helix	53-55	3

Chain D: 13 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	113-140	28
α-helix	145-149	5
α-helix	153-178	26
α-helix	186-219	34
α-helix	224-227	4
α-helix	230-253	24
α-helix	263	1
β-strand	264	1	9
α-helix	265	1
β-strand	272	1	9
α-helix	275-305	31
α-helix	337-356	20
α-helix	358-367	10
α-helix	373-399	27
α-helix	402-411	10

Chain S: 1 helix, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	11-12	2	11
β-strand	17-25	9	10
α-helix	29-31	3
β-strand	33-39	7	12
β-strand	45-51	7	12
β-strand	58-60	3	12
β-strand	68-73	6	10
β-strand	78-84	7	10
β-strand	92-99	8	12
β-strand	111	1	12
β-strand	115-117	3	12
β-strand	118-119	2	11
β-strand	128-129	2	13
β-strand	135-136	2	14
β-strand	143-149	7	13
β-strand	154	1	15
β-strand	160	1	15
β-strand	162-167	6	16
β-strand	174-179	6	16
β-strand	182-183	2	16
β-strand	191-196	6	13
β-strand	199-204	6	13
β-strand	214-219	6	16
β-strand	227	1	16
β-strand	232	1	16
β-strand	233-234	2	14

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)
Cannabinoid receptor 1	D	protein	495	Homo sapiens	P21554 (AlphaFold model)
scFv16	S	protein	259	Mus musculus

Sequence of entity 1 (A), FASTA

>8GHV_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>8GHV_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

>8GHV_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (D), FASTA

>8GHV_4 Cannabinoid receptor 1 (chains D)
DYKDDDDAMKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPLTS
FRGSPFQEKMTAGDNPQLVPADQVNITEFYNKSLSENLYFQGSFKENEENIQCGENFMDI
ECFMVLNPSQQLAIAVLSLTLGTFTVLENLLVLCVILHSRSLRCRPSYHFIGSLAVADLL
GSVIFVYSFIDFHVFHRKDSRNVFLFKLGGVTASFTASVGSLFLTAIDRYISIHRPLAYK
RIVTRPKAVVAFCLMWTIAIVIAVLPLLGWNCEKLQSVCSDIFPHIDETYLMFWIGVTSV
LLLFIVYAYMYILWKAHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMDIRLAKTL
VLILVVLIICWGPLLAIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYALRSKDLR
HAFRSMFPSCEGTAQPLDNSMGDSDCLHKHANNAASVHRAAESCIKSTVKIAKVTMSVST
DTSAEALGSHHHHHH

Sequence of entity 5 (S), FASTA

>8GHV_5 scFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAAHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
ZI5	(5Z,8Z,11Z,13S,14Z)-N-[(2R)-1-hydroxypropan-2-yl]-13-methylicosa-5,8,11,14-tetr…	C24 H41 N O2	1

Primary citation

Structural basis for activation of CB1 by an endocannabinoid analog. Krishna Kumar, K., Robertson, M.J., Thadhani, E. et al. Nat Commun (2023) 14:2672-2672. DOI 10.1038/s41467-023-37864-4 · 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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