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

Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus dehydroepiandrosterone sulfate. Determined by electron microscopy at 2.71 Å resolution. Released 30 Aug 2023.

Method: Electron microscopy
Resolution: 2.71 Å
Organisms: Homo sapiens, Mus musculus
Chains: 9
Atoms: 17,773
Mol. weight: 370.9 kDa
Ligands: NAG, POV, Q3G, PTY
Released: 30 Aug 2023

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

Secondary structure: helices and β-sheets

8SID contains 58 α-helices and 126 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: 10 helices, 17 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	35	1
β-strand	36-51	16	1
β-strand	56-68	13	1
β-strand	82-83	2	1
α-helix	87-89	3
β-strand	96-98	3	2
β-strand	101	1	3
β-strand	106	1	1
β-strand	114-118	5	1
β-strand	123-128	6	1
β-strand	130-132	3	1
β-strand	134	1	3
β-strand	135	1	1
β-strand	147-148	2	2
β-strand	151-156	6	2
β-strand	164-168	5	1
β-strand	175-176	2	1
β-strand	186-199	14	2
β-strand	204-216	13	2
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-240	3
α-helix	247-270	24
α-helix	280-305	26
α-helix	310-339	30

Chain B: 11 helices, 17 β-strands

Element	Residues	Length	Sheet
α-helix	11-22	12
β-strand	39-54	16	4
β-strand	59-69	11	4
β-strand	71	1	5
α-helix	73-75	3
β-strand	83-86	4	4
α-helix	90-92	3
β-strand	99-101	3	6
β-strand	104	1	4
β-strand	108-109	2	4
β-strand	117-122	6	4
β-strand	126	1	5
β-strand	127-138	12	4
β-strand	150-154	5	6
β-strand	157-159	3	6
β-strand	167-171	5	4
α-helix	175-177	3
β-strand	179-181	3	4
β-strand	186	1	4
β-strand	193-204	12	6
β-strand	209-220	12	6
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-242	11
α-helix	243-246	4
α-helix	252-276	25
α-helix	285-310	26
α-helix	315-345	31

Chain C: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	35	1
β-strand	36-51	16	7
β-strand	56-68	13	7
α-helix	70-72	3
β-strand	82-83	2	7
α-helix	87-89	3
β-strand	96-98	3	8
β-strand	101	1	7
β-strand	106	1	7
β-strand	114-118	5	7
β-strand	123-135	13	7
β-strand	147-148	2	8
β-strand	151-156	6	8
β-strand	164-168	5	7
β-strand	175-176	2	7
β-strand	188-200	13	8
β-strand	203-215	13	8
α-helix	216-217	2
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-240	3
α-helix	248-269	22
α-helix	280-304	25
α-helix	310-338	29

Chain D: 11 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	11-23	13
β-strand	39-43	5	9
β-strand	44-54	11	10
β-strand	59-68	10	10
β-strand	71	1	11
α-helix	73-75	3
β-strand	83-86	4	10
α-helix	90-92	3
β-strand	99-101	3	12
β-strand	104	1	10
β-strand	108-109	2	10
β-strand	117-122	6	10
β-strand	126	1	11
β-strand	129-138	10	10
β-strand	152-154	3	12
β-strand	157-159	3	12
β-strand	167-171	5	9
α-helix	175-177	3
β-strand	179-181	3	10
β-strand	186	1	10
β-strand	195-203	9	12
β-strand	210-218	9	12
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-242	11
α-helix	243-245	3
α-helix	252-275	24
α-helix	285-310	26
α-helix	315-345	31

Chain E: 11 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	27-34	8
α-helix	50	1
β-strand	51-57	7	13
β-strand	61-66	6	13
β-strand	71-83	13	13
β-strand	95-98	4	13
α-helix	103-105	3
β-strand	111-113	3	14
β-strand	116-121	6	13
β-strand	129-134	6	13
β-strand	138-150	13	13
β-strand	162-171	10	14
β-strand	179-188	10	13
β-strand	203-214	12	14
β-strand	219-230	12	14
α-helix	231-232	2
α-helix	235-236	2
α-helix	237-241	5
α-helix	242-252	11
α-helix	253-256	4
α-helix	262-286	25
α-helix	296-323	28
α-helix	325-356	32

Chain I: 0 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	15
β-strand	10-12	3	16
β-strand	19-25	7	15
β-strand	33-38	6	16
β-strand	45-48	4	16
β-strand	54	1	16
β-strand	62-65	4	15
β-strand	70-75	6	15
β-strand	85-90	6	16
β-strand	96-97	2	16
β-strand	101-104	4	16

Chain J: 1 helix, 13 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	17
β-strand	10-12	3	18
β-strand	18-19	2	17
β-strand	22-25	4	17
β-strand	34-39	6	18
β-strand	45-51	7	18
β-strand	58	1	18
β-strand	65	1	17
β-strand	68-73	6	17
β-strand	78-83	6	17
α-helix	88-90	3
β-strand	92-98	7	18
β-strand	107-108	2	18
β-strand	112-116	5	18

Chain K: 1 helix, 13 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	21
β-strand	10-12	3	22
β-strand	18-25	8	21
β-strand	34-39	6	23
β-strand	46-52	7	23
β-strand	57-60	4	23
α-helix	62-64	3
β-strand	65	1	21
β-strand	68-73	6	21
β-strand	78-83	6	21
β-strand	93-99	7	23
β-strand	105-108	4	23
β-strand	112-113	2	23
β-strand	114-116	3	22

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

>8SID_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

>8SID_2 Gamma-aminobutyric acid receptor subunit alpha-1 (chains B, D)
QPSLQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEY
TIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLR
ITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVV
VAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVIL
SQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSA
LIEFATVNYFTKSQPARAAKIDRLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 3 (E), FASTA

>8SID_3 Gamma-aminobutyric acid receptor subunit gamma-2 (chains E)
WSHPQFEKGGGSGGGSGGSSAWSHPQFEKLEVLFQGPQKSDDDYEDYASNKTWVLTPKVP
EGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWY
DRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTL
RLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSF
VGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVP
ARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSS
QPARAAKMDSYARIFFPTAFCLFNLVYWVSYLYLSRGSGATNFSLLKQAGDVEENPG

Sequence of entity 4 (I, L), FASTA

>8SID_4 Kappa Fab Light Chain (chains I, L)
NIVMTQSPKSMSMSVGERVTLSCKASEYVGTYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFTGSGSATDFTLTIGSVQAEDLADYHCGQSYSYPTFGAGTKLELKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 5 (J, K), FASTA

>8SID_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
POV	(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl…	C42 H82 N O8 P	1
Q3G	O-[(R)-[(2S)-2-(hexadecanoyloxy)-3-(octadecanoyloxy)propoxy](hydroxy)phosphoryl…	C40 H78 N O10 P	1
PTY	Phosphatidylethanolamine	C40 H80 N O8 P	6
ZWY	17-oxoandrost-5-en-3beta-yl hydrogen sulfate	C19 H28 O5 S	1
ABU	Gamma-amino-butanoic acid	C4 H9 N O2	2

Primary citation

Structural insights into opposing actions of neurosteroids on GABA A receptors. Legesse, D.H., Fan, C., Teng, J. et al. Nat Commun (2023) 14:5091-5091. DOI 10.1038/s41467-023-40800-1 · 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…
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
8DD3 2.9 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus DMCM
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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