8IKH: Human receptor with G proteins

Cryo-EM structure of human receptor with G proteins. Determined by electron microscopy at 3.3 Å resolution. Released 5 Jun 2024.

Method: Electron microscopy
Resolution: 3.3 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,403
Mol. weight: 151.6 kDa
Ligands: Q2L
Released: 5 Jun 2024

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

Secondary structure: helices and β-sheets

8IKH contains 32 α-helices and 58 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	7-27	21
β-strand	33-38	6	1
α-helix	42-46	5
α-helix	47-53	7
β-strand	184-191	8	1
β-strand	194-201	8	1
α-helix	208-210	3
α-helix	213-215	3
β-strand	220-225	6	1
α-helix	242-254	13
β-strand	263-268	6	1
α-helix	271-276	6
α-helix	278-280	3
α-helix	283-286	4
α-helix	296-309	14
β-strand	319-321	3	1
α-helix	331-351	21

Chain B: 5 helices, 31 β-strands

Element	Residues	Length	Sheet
α-helix	4-21	18
α-helix	30-33	4
β-strand	43	1	2
α-helix	45-46	2
β-strand	47-51	5	3
β-strand	58-63	6	4
β-strand	70-74	5	4
β-strand	78-81	4	4
β-strand	91-94	4	4
β-strand	100	1	5
β-strand	104-105	2	6
β-strand	111-115	5	6
β-strand	116	1	5
β-strand	120-125	6	6
α-helix	129-131	3
β-strand	134-140	7	6
β-strand	146-151	6	7
β-strand	157-161	5	7
β-strand	165-168	4	7
β-strand	178-181	4	7
β-strand	187-192	6	8
β-strand	198-203	6	8
β-strand	207-212	6	8
β-strand	218-223	6	8
β-strand	229-234	6	9
β-strand	240-245	6	9
β-strand	250-254	5	9
β-strand	260-264	5	9
β-strand	273-277	5	2
α-helix	280-282	3
β-strand	284-289	6	2
β-strand	294-298	5	2
β-strand	304-308	5	2
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain C: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-22	15
α-helix	30-43	14

Chain R: 12 helices, 0 β-strands

Element	Residues	Length
α-helix	115-117	3
α-helix	118-141	24
α-helix	151-171	21
α-helix	186-219	34
α-helix	224-227	4
α-helix	235-249	15
α-helix	273-278	6
α-helix	282-311	30
α-helix	336-365	30
α-helix	373-387	15
α-helix	389-400	12
α-helix	402-407	6

Chain S: 2 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	10-11	2	11
β-strand	18-25	8	10
α-helix	29-31	3
β-strand	33-39	7	12
β-strand	46-51	6	12
β-strand	60	1	12
β-strand	69-73	5	10
β-strand	78-83	6	10
β-strand	93-95	3	12
β-strand	98-99	2	12
β-strand	115-116	2	12
β-strand	117-118	2	11
α-helix	135-138	4
β-strand	144-148	5	13
β-strand	163	1	14
β-strand	166-167	2	15
β-strand	174	1	15
β-strand	178	1	14
β-strand	192-196	5	13
β-strand	199-203	5	13
β-strand	214-215	2	15
β-strand	226	1	12

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	356	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	R	protein	310	Homo sapiens	P21554 (AlphaFold model)
scFV16	S	protein	266	Mus musculus

Sequence of entity 1 (A), FASTA

>8IKH_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>8IKH_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQ
MRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCA
YAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDT
TCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTG
HESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRL
LLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (C), FASTA

>8IKH_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (R), FASTA

>8IKH_4 Cannabinoid receptor 1 (chains R)
GENFMDIECFMVLNPSQQLAIAVLSLTLGTFTVLENLLVLCVILHSRSLRCRPSYHFIGS
LAVADLLGSVIFVYSFIDFHVFHRKDSRNVFLFKLGGVTASFTASVGSLFLTAIDRYISI
HRPLAYKRIVTRPKAVVAFCLMWTIAIVIAVLPLLGWNCEKLQSVCSDIFPHIDETYLMF
WIGVTSVLLLFIVYAYMYILWKAHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMD
IRLAKTLVLILVVLIICWGPLLAIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYA
LRSKDLRHAF

Sequence of entity 5 (S), FASTA

>8IKH_5 scFV16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAAENLYFQGHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
Q2L	3-[(1R)-1-(2-methoxyphenyl)-2-nitro-ethyl]-2-phenyl-1H-indole	C23 H20 N2 O3	1

Primary citation

Structure-based identification of a G protein-biased allosteric modulator of cannabinoid receptor CB1. Shen, S., Wu, C., Lin, G. et al. Proc Natl Acad Sci U S A (2024) 121:e2321532121-e2321532121. DOI 10.1073/pnas.2321532121 · 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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