8G4X: Gamma-aminobutyric acid receptor subunit alpha-1

Native GABA-A receptor from the mouse brain, meta-alpha1-alpha3-beta2-gamma2 subtype, in complex with GABA and allopregnanolone. Determined by electron microscopy at 2.56 Å resolution. Released 20 Sept 2023.

Method: Electron microscopy
Resolution: 2.56 Å
Organism: Mus musculus
Chains: 7
Atoms: 15,898
Mol. weight: 337.02 kDa
Ligands: Y4B, NAG, ABU, PIO
Released: 20 Sept 2023

Explore 8G4X in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8G4X contains 66 α-helices and 106 β-strands across 7 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: 13 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	12-22	11
α-helix	30	1
β-strand	38-48	11	1
β-strand	49	1	2
β-strand	52-53	2	1
β-strand	58-70	13	1
α-helix	72-74	3
β-strand	82-85	4	1
α-helix	87-90	4
β-strand	98-100	3	3
β-strand	103	1	1
β-strand	107-108	2	1
β-strand	112	1	4
β-strand	116-121	6	1
β-strand	125-137	13	1
β-strand	149-153	5	3
β-strand	156-158	3	3
β-strand	166-170	5	1
α-helix	174-176	3
β-strand	178-180	3	1
β-strand	185	1	2
β-strand	190-203	14	3
β-strand	208-220	13	3
α-helix	223-225	3
α-helix	226-230	5
α-helix	231-240	10
α-helix	243-245	3
α-helix	251-274	24
α-helix	284-309	26
α-helix	386-389	4
α-helix	390-415	26

Chain B: 13 helices, 16 β-strands

Element	Residues	Length	Sheet
α-helix	7-20	14
α-helix	35	1
β-strand	36-41	6	5
β-strand	43	1	6
β-strand	44-51	8	5
β-strand	56-68	13	5
α-helix	70-72	3
β-strand	81-83	3	5
α-helix	85-90	6
β-strand	96-98	3	7
β-strand	101-106	6	5
β-strand	110	1	3
β-strand	114-118	5	5
β-strand	123-135	13	5
α-helix	140-142	3
β-strand	147-156	10	7
β-strand	164-168	5	5
α-helix	171-173	3
β-strand	176	1	6
β-strand	183	1	7
β-strand	186-200	15	7
β-strand	203-216	14	7
α-helix	218-221	4
α-helix	222-226	5
α-helix	227-241	15
α-helix	247-271	25
α-helix	278-279	2
α-helix	280-306	27
α-helix	459-486	28

Chain C: 10 helices, 16 β-strands

Element	Residues	Length	Sheet
α-helix	38-47	10
β-strand	63-73	11	22
β-strand	74	1	23
β-strand	77-78	2	22
β-strand	83-95	13	22
α-helix	97-99	3
β-strand	107-110	4	22
α-helix	112-117	6
β-strand	123-125	3	10
β-strand	128-133	6	22
β-strand	137	1	7
β-strand	141-146	6	22
β-strand	150-162	13	22
α-helix	167-169	3
β-strand	174-183	10	10
β-strand	191-195	5	22
β-strand	203-205	3	22
β-strand	210	1	23
β-strand	215-229	15	10
β-strand	232-245	14	10
α-helix	248-250	3
α-helix	251-255	5
α-helix	256-267	12
α-helix	276-300	25
α-helix	309-334	26
α-helix	426-452	27

Chain D: 11 helices, 17 β-strands

Element	Residues	Length	Sheet
α-helix	26-35	10
α-helix	43	1
β-strand	51-66	16	8
β-strand	71-83	13	8
α-helix	85-87	3
β-strand	95-98	4	8
α-helix	100-105	6
β-strand	111-112	2	9
β-strand	116-121	6	8
β-strand	125	1	10
β-strand	129-134	6	8
β-strand	138-150	13	8
β-strand	162-165	4	11
β-strand	168-169	2	12
β-strand	170-171	2	9
β-strand	179-188	10	8
α-helix	193-195	3
β-strand	201-208	8	11
β-strand	211-215	5	13
β-strand	218-222	5	13
β-strand	223-224	2	12
β-strand	225-231	7	11
α-helix	233-236	4
α-helix	237-241	5
α-helix	242-256	15
α-helix	262-285	24
α-helix	295-318	24
α-helix	411-431	21

Chain E: 13 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	7-20	14
α-helix	28	1
α-helix	35	1
β-strand	36-51	16	14
β-strand	56-68	13	14
α-helix	70-72	3
β-strand	81	1	14
α-helix	85-90	6
β-strand	96-98	3	4
β-strand	101-106	6	14
β-strand	110	1	9
β-strand	114-118	5	14
β-strand	123-135	13	14
α-helix	140-142	3
β-strand	147-156	10	4
β-strand	164-168	5	14
β-strand	176	1	14
β-strand	186-200	15	4
β-strand	203-216	14	4
α-helix	218-221	4
α-helix	222-226	5
α-helix	227-236	10
α-helix	237-241	5
α-helix	247-271	25
α-helix	280-306	27
α-helix	460-487	28

Chain H: 3 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	15
β-strand	10-12	3	16
β-strand	17-23	7	15
α-helix	29-31	3
β-strand	34-39	6	17
β-strand	46-52	7	17
β-strand	56-59	4	17
α-helix	61-63	3
β-strand	64	1	15
β-strand	67-72	6	15
β-strand	77-82A	7	15
α-helix	84-86	3
β-strand	89-94	6	17
β-strand	103	1	17
β-strand	107-108	2	17
β-strand	109-111	3	16

Chain L: 3 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	4-5	2	18
β-strand	10	1	19
α-helix	13-14	2
β-strand	19-23	5	20
β-strand	24-25	2	18
β-strand	33-38	6	21
β-strand	45-49	5	21
β-strand	53-54	2	21
β-strand	62-67	6	20
β-strand	70-75	6	20
α-helix	80-82	3
β-strand	85-90	6	21
β-strand	96-97	2	21
α-helix	98-100	3
β-strand	101	1	21
β-strand	102	1	19

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit alpha-1	A	protein	455	Mus musculus	P62812 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit beta-2	B, E	protein	512	Mus musculus	P63137 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit gamma-2	D	protein	474	Mus musculus	P22723 (AlphaFold model)
Heavy Chain of 8E3 Fab	H	protein	223	Mus musculus
Light Chain of 8E3 Fab	L	protein	213	Mus musculus
Gamma-aminobutyric acid receptor subunit alpha-3	C	protein	492	Mus musculus	P26049 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8G4X_1 Gamma-aminobutyric acid receptor subunit alpha-1 (chains A)
MKKSRGLSDYLWAWTLILSTLSGRSYGQPSQDELKDNTTVFTRILDRLLDGYDNRLRPGL
GERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKI
WTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACP
LKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMT
THFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISAR
NSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDPL
IKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKIDR
LSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 2 (B, E), FASTA

>8G4X_2 Gamma-aminobutyric acid receptor subunit beta-2 (chains B, E)
MWRVRKRGYFGIWSFPLIIAAVCAQSVNDPSNMSLVKETVDRLLKGYDIRLRPDFGGPPV
AVGMNIDIASIDMVSEVNMDYTLTMYFQQAWRDKRLSYNVIPLNLTLDNRVADQLWVPDT
YFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIES
YGYTTDDIEFYWRGDDNAVTGVTKIELPQFSIVDYKLITKKVVFSTGSYPRLSLSFKLKR
NIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIP
YVKAIDMYLMGCFVFVFMALLEYALVNYIFFGRGPQRQKKAAEKAANANNEKMRLDVNKM
FYKDIKQNGTQYRSLWDPTGDLSPTRRTTNYDFSLYTMDPHENILLSTLEIKNEMATSEA
VMGLGDPRSTMLAYDASSIQYRKAGLPRHSFGRNALERHVAQKKSRLRRRASQLKITIPD
LTDVNAIDRWSRIFFPVVFSFFNIVYWLYYVN

Sequence of entity 3 (D), FASTA

>8G4X_3 Gamma-aminobutyric acid receptor subunit gamma-2 (chains D)
MSSPNTWSIGSSVYSPVFSQKMTLWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTPKV
PEGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTW
YDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYT
LRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFS
FVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAV
PARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVS
NRKPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKD
CASFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYL

Sequence of entity 4 (H), FASTA

>8G4X_4 Heavy Chain of 8E3 Fab (chains H)
EIQLQQSGPELVKPGTSVKVSCKASGYSFTDYNMYWVKQSHGKSLEWIGYIDPYNADTTY
NREFKGKATLTVDKSSSTAFMHLNSLTSEDSAVYYCARKRNNFYFDYWGQGTPLTVSSAK
TTPPSVYPLAPGCGDTTGSSVTLGCLVKGYFPESVTVTWNSGSLSSSVHTFPALLQSGLY
TMSSSVTVPSSTWPSQTVTCSVAHPASSTTVDKKSAALEVLFQ

Sequence of entity 5 (L), FASTA

>8G4X_5 Light Chain of 8E3 Fab (chains L)
YIVMTQSPKSMSMSLGERVTLSCRASEYVGSYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFAGSGSATDFTLTITSVQAEDLADYHCGQTYNYPTFGGGTKLEIKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 6 (C), FASTA

>8G4X_6 Gamma-aminobutyric acid receptor subunit alpha-3 (chains C)
MIITQMWHFYVTRVVLLLLISILPGTTSQGESRRQEPGDFVKQDIGGLSPKHAPDIPDDS
TDNITIFTRILDRLLDGYDNRLRPGLGDAVTEVKTDIYVTSFGPVSDTDMEYTIDVFFRQ
TWHDERLKFDGPMKILPLNNLLASKIWTPDTFFHNGKKSVAHNMTTPNKLLRLVDNGTLL
YTMRLTIHAECPMHLEDFPMDVHACPLKFGSYAYTKAEVIYSWTLGKNKSVEVAQDGSRL
NQYDLLGHVVGTEIIRSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLN
RESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVN
YFTKRSWAWEGKKVPEALEMKKKTPAAPTKKNTTFNIVGTTYPINLAKDTEFSTISKSAA
APSASSTPTAIASPKATYVQDSPAETKTYNSVSKVDKISRIIFPVLFAIFNLVYWATYVN
RESAIKGMIRKQ

Ligands and cofactors

ID	Name	Formula	Copies
Y4B	allopregnanolone	C21 H34 O2	2
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1
ABU	Gamma-amino-butanoic acid	C4 H9 N O2	2
PIO	[(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-d…	C25 H49 O19 P3	2

Primary citation

Cryo-EM structures reveal native GABA A receptor assemblies and pharmacology. Sun, C., Zhu, H., Clark, S. et al. Nature (2023) 622:195-201. DOI 10.1038/s41586-023-06556-w · PubMed

Other PDB entries of the same protein (UniProt P62812 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8FOI 2.5 Å, Native GABA-A receptor from the mouse brain, alpha1-beta2-gamma2 subtype, in complex…
8G5F 2.64 Å, Native GABA-A receptor from the mouse brain, ortho-alpha1-alpha3-beta2-gamma2 subtype,…
8G4N 2.67 Å, Native GABA-A receptor from the mouse brain, alpha1-beta2-gamma2 subtype, in complex…
5OSA 2.75 Å, GLIC-GABAAR alpha1 chimera crystallized at pH4.6
8G5H 2.89 Å, Native GABA-A receptor from the mouse brain, ortho-alpha1-alpha3-beta2-gamma2 subtype,…
8G5G 2.94 Å, Native GABA-A receptor from the mouse brain, meta-alpha1-alpha3-beta2-gamma2 subtype, in…
8G4O 3.06 Å, Native GABA-A receptor from the mouse brain, alpha1-beta2-gamma2 subtype, in complex…
5OSC 3.1 Å, GLIC-GABAAR alpha1 chimera crystallized in complex with pregnenolone sulfate at pH 4.5
5OSB 3.8 Å, GLIC-GABAAR alpha1 chimera crystallized in complex with THDOC at pH4.5

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