8DD3: Human GABAA receptor alpha1-beta2-gamma2 subtype

Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus DMCM. Determined by electron microscopy at 2.9 Å resolution. Released 17 Aug 2022.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Homo sapiens, Mus musculus
Chains: 9
Atoms: 17,459
Mol. weight: 365.55 kDa
Ligands: NAG, R63, ABU
Released: 17 Aug 2022

Explore 8DD3 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8DD3 contains 65 α-helices and 114 β-strands across 9 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: 14 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	35	1
β-strand	36-46	11	1
β-strand	50-51	2	1
β-strand	56-68	13	1
α-helix	70-72	3
β-strand	82-83	2	1
α-helix	85-89	5
β-strand	96-98	3	2
β-strand	101-106	6	1
β-strand	114-118	5	1
β-strand	123-135	13	1
α-helix	137-139	3
β-strand	147-150	4	2
β-strand	153-156	4	2
β-strand	164-168	5	1
α-helix	171-174	4
β-strand	175-176	2	1
β-strand	186-200	15	2
β-strand	203-216	14	2
α-helix	218-221	4
α-helix	222-226	5
α-helix	227-241	15
α-helix	247-269	23
α-helix	273-274	2
α-helix	278-279	2
α-helix	280-306	27
α-helix	310-338	29

Chain B: 10 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	13-23	11
β-strand	39-54	16	3
β-strand	59-71	13	3
α-helix	73-75	3
β-strand	83-86	4	3
β-strand	99-101	3	4
β-strand	104-109	6	3
β-strand	113	1	2
β-strand	117-122	6	3
β-strand	126-138	13	3
β-strand	150-159	10	4
β-strand	167-171	5	3
α-helix	175-177	3
β-strand	179-181	3	3
β-strand	186	1	3
β-strand	191-204	14	4
β-strand	209-221	13	4
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-243	12
α-helix	244-246	3
α-helix	252-274	23
α-helix	285-310	26
α-helix	315-346	32

Chain C: 11 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	35	1
β-strand	36-51	16	5
β-strand	56-68	13	5
α-helix	70-72	3
β-strand	82-83	2	5
α-helix	85-89	5
β-strand	96-98	3	6
β-strand	101-106	6	5
β-strand	114-118	5	5
β-strand	123-135	13	5
α-helix	137-139	3
β-strand	147-156	10	6
β-strand	164-168	5	5
β-strand	175-176	2	5
β-strand	186-200	15	6
β-strand	203-216	14	6
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-241	15
α-helix	247-271	25
α-helix	280-305	26
α-helix	310-339	30

Chain D: 13 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	13-23	11
β-strand	39-49	11	7
β-strand	53-54	2	7
β-strand	59-71	13	7
α-helix	73-75	3
β-strand	83-86	4	7
α-helix	88-92	5
β-strand	99-101	3	8
β-strand	104	1	7
β-strand	108-109	2	7
β-strand	117-122	6	7
β-strand	126-138	13	7
α-helix	143-145	3
β-strand	150-159	10	8
β-strand	167-171	5	7
α-helix	175-177	3
β-strand	179-181	3	7
β-strand	191-205	15	8
β-strand	208-221	14	8
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-243	12
α-helix	244-246	3
α-helix	252-274	23
α-helix	278-279	2
α-helix	285-310	26
α-helix	315-345	31

Chain E: 10 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	26-35	10
α-helix	50	1
β-strand	51-53	3	9
β-strand	56-66	11	10
β-strand	71-83	13	10
α-helix	85-87	3
β-strand	95-98	4	10
α-helix	100-102	3
β-strand	111-113	3	11
β-strand	116-121	6	10
β-strand	125	1	8
β-strand	129-134	6	10
β-strand	138-150	13	10
β-strand	163-171	9	11
β-strand	179-181	3	9
β-strand	188-190	3	10
β-strand	201-214	14	11
β-strand	219-231	13	11
α-helix	234-236	3
α-helix	237-241	5
α-helix	242-256	15
α-helix	262-285	24
α-helix	295-323	29
α-helix	325-356	32

Chain I: 1 helix, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	12
β-strand	10-12	3	13
β-strand	19-25	7	12
β-strand	33-38	6	14
β-strand	45-49	5	14
β-strand	53-54	2	14
α-helix	55	1
β-strand	62-65	4	12
β-strand	70-75	6	12
β-strand	85-90	6	14
β-strand	96-97	2	14
β-strand	101	1	14
β-strand	102-104	3	13

Chain J: 1 helix, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	15
β-strand	10-12	3	16
β-strand	18-25	8	15
α-helix	29-31	3
β-strand	34-39	6	16
β-strand	46-52	7	16
β-strand	57-60	4	16
β-strand	68-73	6	15
β-strand	78-83	6	15
β-strand	92-97	6	16
β-strand	108	1	16
β-strand	112-116	5	16

Chain K: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	20
β-strand	10-12	3	21
β-strand	18-25	8	20
α-helix	29-31	3
β-strand	34-39	6	21
β-strand	46-52	7	21
β-strand	57-60	4	21
α-helix	62-64	3
β-strand	65	1	20
β-strand	68-73	6	20
β-strand	78-83	6	20
α-helix	88-90	3
β-strand	92-99	8	21
β-strand	105-108	4	21
β-strand	112-116	5	21

1 more chain groups are not listed. Open the entry in the viewer and use the sequence panel to see them.

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit beta-2	A, C	protein	364	Homo sapiens	P47870 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit alpha-1	B, D	protein	358	Homo sapiens	P14867 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit gamma-2	E	protein	417	Homo sapiens	P18507 (AlphaFold model)
Kappa Fab Light Chain	I, L	protein	213	Mus musculus
IgG2b Fab Heavy Chain	J, K	protein	454	Mus musculus

Sequence of entity 1 (A, C), FASTA

>8DD3_1 Gamma-aminobutyric acid receptor subunit beta-2 (chains A, C)
QSVNDPSNMSLVKETVDRLLKGYDIRLRPDFGGPPVAVGMNIDIASIDMVSEVNMDYTLT
MYFQQAWRDKRLSYNVIPLNLTLDNRVADQLWVPDTYFLNDKKSFVHGVTVKNRMIRLHP
DGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIESYGYTTDDIEFYWRGDDNAVTGVTK
IELPQFSIVDYKLITKKVVFSTGSYPRLSLSFKLKRNIGYFILQTYMPSILITILSWVSF
WINYDASAARVALGITTVLTMTTINTHLRETLPKIPYVKAIDMYLMGCFVFVFMALLEYA
LVNYIFFSQPARAAAIDRWSRIFFPVVFSFFNIVYWLYYVNVDGSGATNFSLLKQAGDVE
ENPG

Sequence of entity 2 (B, D), FASTA

>8DD3_2 Gamma-aminobutyric acid receptor subunit alpha-1 (chains B, D)
QPSLQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEY
TIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLR
ITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVV
VAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVIL
SQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSA
LIEFATVNYFTKSQPARAAKIDRLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 3 (E), FASTA

>8DD3_3 Gamma-aminobutyric acid receptor subunit gamma-2 (chains E)
WSHPQFEKGGGSGGGSGGSSAWSHPQFEKLEVLFQGPQKSDDDYEDYASNKTWVLTPKVP
EGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWY
DRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTL
RLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSF
VGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVP
ARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSS
QPARAAKMDSYARIFFPTAFCLFNLVYWVSYLYLSRGSGATNFSLLKQAGDVEENPG

Sequence of entity 4 (I, L), FASTA

>8DD3_4 Kappa Fab Light Chain (chains I, L)
NIVMTQSPKSMSMSVGERVTLSCKASEYVGTYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFTGSGSATDFTLTIGSVQAEDLADYHCGQSYSYPTFGAGTKLELKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 5 (J, K), FASTA

>8DD3_5 IgG2b Fab Heavy Chain (chains J, K)
EVQLQQSGAELVKPGASVKLSCTASGFNIKDTYMYWVKQRPEQGLEWIGRIDPANGDTKY
DPKFQGKATITTDTFSNTAYLQLSSLTSEDTAVYYCARKGLRWAMDYWGQGTSVTVSTAK
TTPPSVYPLAPGCGDTTGSSVTLGCLVKGYFPESVTVTWNSGSLSSSVHTFPALLQSGLY
TMSSSVTVPSSTWPSQTVTCSVAHPASSTTVDKKLEPSGPISTINPCPPCKECHKCPAPN
LEGGPSVFIFPPNIKDVLMISLTPKVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQTHR
EDYNSTIRVVSTLPIQHQDWMSGKEFKCKVNNKDLPSPIERTISKIKGLVRAPQVYILPP
PAEQLSRKDVSLTCLVVGFNPGDISVEWTSNGHTEENYKDTAPVLDSDGSYFIYSKLNMK
TSKWEKTDSFSCNVRHEGLKNYYLKKTISRSPGK

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	2
R63	methyl 4-ethyl-6,7-dimethoxy-9H-pyrido[3,4-b]indole-3-carboxylate	C17 H18 N2 O4	3
ABU	Gamma-amino-butanoic acid	C4 H9 N O2	2

Primary citation

Structural and dynamic mechanisms of GABA A receptor modulators with opposing activities. Zhu, S., Sridhar, A., Teng, J. et al. Nat Commun (2022) 13:4582-4582. DOI 10.1038/s41467-022-32212-4 · PubMed

Other PDB entries of the same protein (UniProt P47870 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6X3T 2.55 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus propofol
8VRN 2.57 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus PPTQ
8SGO 2.65 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus pregnenolone…
8SID 2.71 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus…
8VQY 2.82 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus methaqualone
6X40 2.86 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus picrotoxin
8DD2 2.9 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus Zolpidem
9CRS 2.9 Å, Native human GABAA receptor of beta2-alpha1-beta2-alpha1-gamma2 assembly
6X3X 2.92 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus diazepam
9DRX 2.95 Å, Human GABAA receptor of beta2-alpha1-beta2-alpha1-gamma2 subtype in complex with GABA…
8SI9 2.98 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus…
7T0W 3.0 Å, Complex of GABA-A synaptic receptor with autoimmune antibody Fab115

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