23IV: Cannabinoid Receptor 1-Gi Complex

Cannabinoid Receptor 1-Gi Complex. Determined by electron microscopy at 2.42 Å resolution. Released 20 May 2026.

Method: Electron microscopy
Resolution: 2.42 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,625
Mol. weight: 169.15 kDa
Ligands: A1E5S
Released: 20 May 2026

Explore 23IV in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

23IV contains 35 α-helices and 63 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, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	33-40	8	1
α-helix	46-53	8
β-strand	185-190	6	1
β-strand	195-200	6	1
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	1
α-helix	227-229	3
α-helix	242-254	13
α-helix	257-259	3
β-strand	263-269	7	1
α-helix	271-280	10
α-helix	283-285	3
α-helix	296-306	11
β-strand	319-322	4	1
α-helix	331-351	21

Chain B: 3 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	3-25	23
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	88-94	7	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	120	1	5
β-strand	122-125	4	4
β-strand	134-137	4	4
β-strand	140	1	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	166-170	5	6
β-strand	175-180	6	6
β-strand	187-192	6	7
β-strand	198-203	6	7
β-strand	207-212	6	7
β-strand	218-223	6	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	249-254	6	8
β-strand	259-264	6	8
α-helix	272	1
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	294-298	5	9
β-strand	304-308	5	9
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain D: 12 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	105-107	3
α-helix	113-142	30
α-helix	145-149	5
α-helix	151-178	28
α-helix	188-219	32
α-helix	224-227	4
α-helix	230-253	24
β-strand	264	1	16
β-strand	272	1	16
α-helix	275-308	34
α-helix	337-354	18
α-helix	357-367	11
α-helix	373-397	25
α-helix	402-411	10

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	30-43	14
α-helix	53-55	3
α-helix	56-58	3

Chain S: 5 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	11-12	2	11
β-strand	18-25	8	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	78-83	6	10
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	110-111	2	12
β-strand	115-117	3	12
β-strand	118-119	2	11
α-helix	125-127	3
β-strand	128-129	2	13
β-strand	134-136	3	14
β-strand	143-149	7	13
β-strand	154	1	15
β-strand	160	1	15
β-strand	162-167	6	14
β-strand	173-178	6	14
β-strand	182-183	2	14
α-helix	184	1
β-strand	191-195	5	13
β-strand	199-204	6	13
β-strand	213-219	7	14
α-helix	225	1
β-strand	227	1	14
β-strand	231-234	4	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	339	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
Scfv16	S	protein	250	Mus musculus
Cannabinoid receptor 1	D	protein	504	Homo sapiens	P21554 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>23IV_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>23IV_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
SELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAM
HWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNIC
SIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFT
GHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAF
ATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALK
ADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>23IV_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (S), FASTA

>23IV_4 Scfv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGS

Sequence of entity 5 (D), FASTA

>23IV_5 Cannabinoid receptor 1 (chains D)
MKTIIALSYIFCLVFADYKDDDDKLEVLFQGPMKSILDGLADTTFRTITTDLLYVGSNDI
QYEDIKGDMASKLGYFPQKFPLTSFRGSPFQEKMTAGDNPQLVPADQVNITEFYNKSLSS
FKENEENIQCGENFMDIECFMVLNPSQQLAIAVLSLTLGTFTVLENLLVLCVILHSRSLR
CRPSYHFIGSLAVADLLGSVIFVYSFIDFHVFHRKDSRNVFLFKLGGVTASFTASVGSLF
LTAIDRYISIHRPLAYKRIVTRPKAVVAFCLMWTIAIVIAVLPLLGWNCEKLQSVCSDIF
PHIDETYLMFWIGVTSVLLLFIVYAYMYILWKAHSHAVRMIQRGTQKSIIIHTSEDGKVQ
VTRPDQARMDIRLAKTLVLILVVLIICWGPLLAIMVYDVFGKMNKLIKTVFAFCSMLCLL
NSTVNPIIYALRSKDLRHAFRSMFPSCEGTAQPLDNSMGDSDCLHKHANNAASVHRAAES
CIKSTVKIAKVTMSVSTDTSAEAL

Ligands and cofactors

ID	Name	Formula	Copies
A1E5S	methyl 1-[[1-[(4-fluorophenyl)methyl]indazol-3-yl]carbonylamino]cyclopropane-1-…	C20 H18 F N3 O3	1

Primary citation

Rational design of G i -biased CB1 agonist with reduced side effects. Liao, Y.Y., Che, J., Gao, Y.T. et al. Cell (2026) 189:3432. DOI 10.1016/j.cell.2026.03.020 · 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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