8G5H: Gamma-aminobutyric acid receptor subunit beta-2

Native GABA-A receptor from the mouse brain, ortho-alpha1-alpha3-beta2-gamma2 subtype, in complex with GABA, Zolpidem, and endogenous neurosteroid. Determined by electron microscopy at 2.89 Å resolution. Released 20 Sept 2023.

Method: Electron microscopy
Resolution: 2.89 Å
Organism: Mus musculus
Chains: 7
Atoms: 15,875
Mol. weight: 337.66 kDa
Ligands: PIO, NAG, Y4B, R5R
Released: 20 Sept 2023

Explore 8G5H in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8G5H contains 65 α-helices and 97 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: 11 helices, 15 β-strands

Element	Residues	Length	Sheet
α-helix	38-47	10
α-helix	55	1
β-strand	63-78	16	19
β-strand	83-95	13	19
β-strand	107-110	4	19
α-helix	114-117	4
β-strand	123-124	2	20
β-strand	128-133	6	19
β-strand	141-146	6	19
β-strand	150-162	13	19
β-strand	176-177	2	21
β-strand	182-183	2	20
β-strand	191-195	5	19
β-strand	203-205	3	19
β-strand	215	1	22
β-strand	219-228	10	21
β-strand	233-242	10	21
β-strand	245	1	22
α-helix	248-250	3
α-helix	251-255	5
α-helix	256-270	15
α-helix	276-300	25
α-helix	309-333	25
α-helix	339-341	3
α-helix	423-425	3
α-helix	426-450	25

Chain B: 14 helices, 17 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	28	1
α-helix	35	1
β-strand	36-41	6	1
β-strand	42-43	2	2
β-strand	44-46	3	3
β-strand	50-51	2	3
β-strand	56-61	6	3
β-strand	64-67	4	1
α-helix	70-72	3
β-strand	81-83	3	1
α-helix	85-90	6
β-strand	96-98	3	4
β-strand	103-106	4	3
β-strand	114-118	5	1
β-strand	124-128	5	1
β-strand	130-135	6	3
β-strand	147-156	10	4
β-strand	164-168	5	1
α-helix	171-173	3
β-strand	175-176	2	2
β-strand	186-200	15	4
β-strand	203-216	14	4
α-helix	218-221	4
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-241	4
α-helix	247-271	25
α-helix	278-279	2
α-helix	280-307	28
α-helix	459-486	28

Chain C: 12 helices, 15 β-strands

Element	Residues	Length	Sheet
α-helix	10-22	13
α-helix	30	1
β-strand	38-48	11	5
α-helix	50-51	2
β-strand	52-53	2	5
β-strand	58-70	13	5
β-strand	82-85	4	5
α-helix	87-90	4
β-strand	98-100	3	6
β-strand	103	1	5
β-strand	107-108	2	5
β-strand	116-121	6	5
β-strand	125-137	13	5
β-strand	149-153	5	7
β-strand	156-158	3	6
β-strand	166-170	5	5
α-helix	174-176	3
β-strand	178-180	3	5
β-strand	190-203	14	7
β-strand	208-220	13	7
α-helix	223-225	3
α-helix	226-230	5
α-helix	231-245	15
α-helix	251-274	24
α-helix	284-309	26
α-helix	386-389	4
α-helix	390-415	26

Chain D: 12 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	26-35	10
α-helix	43	1
α-helix	50	1
β-strand	51-66	16	8
β-strand	71-83	13	8
β-strand	95-98	4	8
α-helix	100-105	6
β-strand	112	1	9
β-strand	118-121	4	8
β-strand	129-134	6	8
β-strand	138-150	13	8
β-strand	162-165	4	10
β-strand	170	1	9
β-strand	179-188	10	8
α-helix	193-195	3
β-strand	201-215	15	10
β-strand	218-231	14	10
α-helix	235-236	2
α-helix	237-241	5
α-helix	242-256	15
α-helix	262-286	25
α-helix	293-294	2
α-helix	295-318	24
α-helix	411-431	21

Chain E: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	8-20	13
α-helix	28	1
α-helix	35	1
β-strand	36-41	6	11
β-strand	42-43	2	12
β-strand	44-51	8	11
β-strand	56-68	13	11
β-strand	81-83	3	11
α-helix	85-90	6
α-helix	93-95	3
β-strand	97-98	2	13
β-strand	101-106	6	11
β-strand	114-118	5	11
β-strand	123-135	13	11
β-strand	147-155	9	13
β-strand	164-168	5	11
β-strand	175-176	2	12
β-strand	186-200	15	13
β-strand	203-216	14	13
α-helix	218-221	4
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-241	4
α-helix	247-269	23
α-helix	280-306	27
α-helix	460-486	27

Chain J: 2 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	4	1	14
β-strand	5-6	2	15
α-helix	7-9	3
β-strand	10-11	2	16
β-strand	18-23	6	15
β-strand	34-39	6	16
β-strand	45-51	7	16
β-strand	57-59	3	16
β-strand	64	1	15
β-strand	67-72	6	15
β-strand	77-82	6	15
α-helix	84-86	3
β-strand	88-94	7	16
β-strand	103	1	16
β-strand	104	1	14
β-strand	107-110	4	16

Chain K: 2 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	2-3	2
β-strand	4-5	2	17
β-strand	10-12	3	18
β-strand	19-25	7	17
β-strand	34-38	5	18
β-strand	45-48	4	18
α-helix	53-55	3
β-strand	62-66	5	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

Molecules and chains

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

Sequence of entity 1 (B, E), FASTA

>8G5H_1 Gamma-aminobutyric acid receptor subunit beta-2 (chains B, E)
MWRVRKRGYFGIWSFPLIIAAVCAQSVNDPSNMSLVKETVDRLLKGYDIRLRPDFGGPPV
AVGMNIDIASIDMVSEVNMDYTLTMYFQQAWRDKRLSYNVIPLNLTLDNRVADQLWVPDT
YFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIES
YGYTTDDIEFYWRGDDNAVTGVTKIELPQFSIVDYKLITKKVVFSTGSYPRLSLSFKLKR
NIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIP
YVKAIDMYLMGCFVFVFMALLEYALVNYIFFGRGPQRQKKAAEKAANANNEKMRLDVNKM
FYKDIKQNGTQYRSLWDPTGDLSPTRRTTNYDFSLYTMDPHENILLSTLEIKNEMATSEA
VMGLGDPRSTMLAYDASSIQYRKAGLPRHSFGRNALERHVAQKKSRLRRRASQLKITIPD
LTDVNAIDRWSRIFFPVVFSFFNIVYWLYYVN

Sequence of entity 2 (C), FASTA

>8G5H_2 Gamma-aminobutyric acid receptor subunit alpha-1 (chains C)
MKKSRGLSDYLWAWTLILSTLSGRSYGQPSQDELKDNTTVFTRILDRLLDGYDNRLRPGL
GERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKI
WTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACP
LKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMT
THFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISAR
NSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDPL
IKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKIDR
LSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 3 (D), FASTA

>8G5H_3 Gamma-aminobutyric acid receptor subunit gamma-2 (chains D)
MSSPNTWSIGSSVYSPVFSQKMTLWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTPKV
PEGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTW
YDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYT
LRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFS
FVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAV
PARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVS
NRKPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKD
CASFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYL

Sequence of entity 4 (J), FASTA

>8G5H_4 Heavy Chain of 8E3 Fab (chains J)
EIQLQQSGPELVKPGTSVKVSCKASGYSFTDYNMYWVKQSHGKSLEWIGYIDPYNADTTY
NREFKGKATLTVDKSSSTAFMHLNSLTSEDSAVYYCARKRNNFYFDYWGQGTPLTVSSAK
TTPPSVYPLAPGCGDTTGSSVTLGCLVKGYFPESVTVTWNSGSLSSSVHTFPALLQSGLY
TMSSSVTVPSSTWPSQTVTCSVAHPASSTTVDKKSAALEVLFQ

Sequence of entity 5 (K), FASTA

>8G5H_5 Light Chain of 8E3 Fab (chains K)
YIVMTQSPKSMSMSLGERVTLSCRASEYVGSYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFAGSGSATDFTLTITSVQAEDLADYHCGQTYNYPTFGGGTKLEIKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 6 (A), FASTA

>8G5H_6 Gamma-aminobutyric acid receptor subunit alpha-3 (chains A)
MIITQMWHFYVTRVVLLLLISILPGTTSQGESRRQEPGDFVKQDIGGLSPKHAPDIPDDS
TDNITIFTRILDRLLDGYDNRLRPGLGDAVTEVKTDIYVTSFGPVSDTDMEYTIDVFFRQ
TWHDERLKFDGPMKILPLNNLLASKIWTPDTFFHNGKKSVAHNMTTPNKLLRLVDNGTLL
YTMRLTIHAECPMHLEDFPMDVHACPLKFGSYAYTKAEVIYSWTLGKNKSVEVAQDGSRL
NQYDLLGHVVGTEIIRSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLN
RESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVN
YFTKRSWAWEGKKVPEALEMKKKTPAAPTKKNTTFNIVGTTYPINLAKDTEFSTISKSAA
APSASSTPTAIASPKATYVQDSPAETKTYNSVSKVDKISRIIFPVLFAIFNLVYWATYVN
RESAIKGMIRKQ

Ligands and cofactors

ID	Name	Formula	Copies
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
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1
Y4B	allopregnanolone	C21 H34 O2	1
R5R	Zolpidem	C19 H21 N3 O	1
ABU	Gamma-amino-butanoic acid	C4 H9 N O2	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 P63137 (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…
8G4X 2.56 Å, Native GABA-A receptor from the mouse brain, meta-alpha1-alpha3-beta2-gamma2 subtype, in…
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…
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…

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