8SI9: Human GABAA receptor alpha1-beta2-gamma2 subtype

Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus allopregnanolone. Determined by electron microscopy at 2.98 Å resolution. Released 30 Aug 2023.

Method: Electron microscopy
Resolution: 2.98 Å
Organisms: Homo sapiens, Mus musculus
Chains: 9
Atoms: 17,420
Mol. weight: 365.24 kDa
Ligands: NAG, Y4B, ABU
Released: 30 Aug 2023

Explore 8SI9 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8SI9 contains 59 α-helices and 128 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: 11 helices, 19 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	35	1
β-strand	36-41	6	1
β-strand	42-43	2	2
β-strand	44-51	8	3
β-strand	56-61	6	3
β-strand	64-68	5	1
β-strand	82-83	2	1
α-helix	87-89	3
β-strand	96-98	3	4
β-strand	101	1	5
β-strand	106	1	3
β-strand	114-118	5	1
β-strand	123-128	6	1
β-strand	130-132	3	3
β-strand	134	1	5
β-strand	135	1	3
β-strand	147-156	10	4
β-strand	164-168	5	1
β-strand	175-176	2	2
β-strand	186-199	14	4
β-strand	204-216	13	4
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	280-304	25
α-helix	312-319	8
α-helix	323-339	17

Chain B: 12 helices, 17 β-strands

Element	Residues	Length	Sheet
α-helix	12-22	11
β-strand	39-54	16	6
β-strand	59-69	11	6
β-strand	71	1	7
α-helix	73-75	3
β-strand	84-86	3	6
α-helix	90-92	3
β-strand	99-101	3	8
β-strand	104	1	6
β-strand	108-109	2	6
β-strand	117-121	5	6
β-strand	126	1	7
β-strand	127-138	12	6
β-strand	150-154	5	8
β-strand	157-159	3	8
β-strand	167-171	5	6
α-helix	175-177	3
β-strand	179-181	3	6
β-strand	186	1	6
β-strand	193-204	12	8
β-strand	209-220	12	8
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-243	12
α-helix	244-246	3
α-helix	252-272	21
α-helix	273-276	4
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	9
β-strand	56-68	13	9
α-helix	70-72	3
β-strand	82-83	2	9
α-helix	87-90	4
β-strand	96-98	3	10
β-strand	101	1	9
β-strand	106	1	9
β-strand	114-118	5	9
β-strand	123-135	13	9
β-strand	147-148	2	10
β-strand	151-156	6	10
β-strand	164-168	5	9
β-strand	175-176	2	9
β-strand	188-200	13	10
β-strand	203-215	13	10
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	248-271	24
α-helix	280-304	25
α-helix	310-338	29

Chain D: 11 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	13-23	11
β-strand	39-43	5	11
β-strand	44-50	7	12
β-strand	59-68	10	12
β-strand	71	1	13
α-helix	73-75	3
β-strand	83-86	4	12
α-helix	90-92	3
β-strand	99-101	3	14
β-strand	104	1	12
β-strand	108-109	2	12
β-strand	117-122	6	12
β-strand	126	1	13
β-strand	129-138	10	12
β-strand	152-154	3	14
β-strand	157-159	3	14
β-strand	167-171	5	11
α-helix	175-177	3
β-strand	179-181	3	12
β-strand	186	1	12
β-strand	195-203	9	14
β-strand	210-218	9	14
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-242	11
α-helix	243-245	3
α-helix	252-274	23
α-helix	285-310	26
α-helix	315-345	31

Chain E: 10 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	27-34	8
α-helix	50	1
β-strand	51-57	7	15
β-strand	61-66	6	15
β-strand	71-83	13	15
β-strand	95-98	4	15
α-helix	103-105	3
β-strand	111-113	3	16
β-strand	116-121	6	15
β-strand	129-134	6	15
β-strand	138-150	13	15
β-strand	162-171	10	16
β-strand	179-188	10	15
β-strand	203-214	12	16
β-strand	219-230	12	16
α-helix	235-236	2
α-helix	237-241	5
α-helix	242-252	11
α-helix	253-255	3
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	17
β-strand	10-12	3	18
β-strand	19-25	7	17
β-strand	33-38	6	18
β-strand	45-48	4	18
β-strand	54	1	18
β-strand	62-65	4	17
β-strand	70-75	6	17
β-strand	85-90	6	18
β-strand	96-97	2	18
β-strand	101-104	4	18

Chain J: 1 helix, 13 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	19
β-strand	10-12	3	20
β-strand	18-19	2	19
β-strand	22-25	4	19
β-strand	34-39	6	20
β-strand	45-51	7	20
β-strand	58	1	20
β-strand	65	1	19
β-strand	68-73	6	19
β-strand	78-83	6	19
α-helix	88-90	3
β-strand	92-98	7	20
β-strand	107-108	2	20
β-strand	112-116	5	20

Chain K: 1 helix, 13 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	23
β-strand	10-12	3	24
β-strand	18-25	8	23
β-strand	34-39	6	25
β-strand	46-52	7	25
β-strand	57-60	4	25
α-helix	62-64	3
β-strand	65	1	23
β-strand	68-73	6	23
β-strand	78-83	6	23
β-strand	93-99	7	25
β-strand	105-108	4	25
β-strand	112-113	2	25
β-strand	114-116	3	24

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

>8SI9_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

>8SI9_2 Gamma-aminobutyric acid receptor subunit alpha-1 (chains B, D)
QPSLQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEY
TIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLR
ITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVV
VAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVIL
SQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSA
LIEFATVNYFTKSQPARAAKIDRLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 3 (E), FASTA

>8SI9_3 Gamma-aminobutyric acid receptor subunit gamma-2 (chains E)
WSHPQFEKGGGSGGGSGGSSAWSHPQFEKLEVLFQGPQKSDDDYEDYASNKTWVLTPKVP
EGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWY
DRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTL
RLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSF
VGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVP
ARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSS
QPARAAKMDSYARIFFPTAFCLFNLVYWVSYLYLSRGSGATNFSLLKQAGDVEENPG

Sequence of entity 4 (I, L), FASTA

>8SI9_4 Kappa Fab Light Chain (chains I, L)
NIVMTQSPKSMSMSVGERVTLSCKASEYVGTYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFTGSGSATDFTLTIGSVQAEDLADYHCGQSYSYPTFGAGTKLELKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 5 (J, K), FASTA

>8SI9_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
Y4B	allopregnanolone	C21 H34 O2	2
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…
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
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…
7T0W 3.0 Å, Complex of GABA-A synaptic receptor with autoimmune antibody Fab115

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