8G5F: Gamma-aminobutyric acid receptor subunit alpha-3

Native GABA-A receptor from the mouse brain, ortho-alpha1-alpha3-beta2-gamma2 subtype, in complex with GABA and allopregnanolone. Determined by electron microscopy at 2.64 Å resolution. Released 20 Sept 2023.

Method: Electron microscopy
Resolution: 2.64 Å
Organism: Mus musculus
Chains: 7
Atoms: 15,762
Mol. weight: 335.51 kDa
Ligands: Y4B, ABU, PIO
Released: 20 Sept 2023

Explore 8G5F in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8G5F contains 66 α-helices and 101 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, 16 β-strands

Element	Residues	Length	Sheet
α-helix	38-45	8
α-helix	55	1
β-strand	63-78	16	1
β-strand	83-95	13	1
α-helix	97-99	3
β-strand	107-110	4	1
α-helix	112-117	6
β-strand	123-125	3	2
β-strand	128	1	1
β-strand	132-133	2	1
β-strand	137	1	3
β-strand	141-146	6	1
β-strand	150-162	13	1
β-strand	174-177	4	2
β-strand	181-183	3	2
β-strand	191-195	5	1
β-strand	203-205	3	1
β-strand	210	1	1
β-strand	215-228	14	2
β-strand	233-245	13	2
α-helix	248-250	3
α-helix	251-255	5
α-helix	256-270	15
α-helix	276-300	25
α-helix	309-334	26
α-helix	422-425	4
α-helix	426-452	27

Chain B: 14 helices, 16 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	28	1
α-helix	35	1
β-strand	36-41	6	4
β-strand	42-43	2	5
β-strand	44-46	3	4
β-strand	50-51	2	4
β-strand	56-68	13	4
α-helix	70-72	3
β-strand	81-83	3	4
α-helix	85-90	6
β-strand	96-98	3	6
β-strand	101-106	6	4
β-strand	110	1	2
β-strand	114-118	5	4
β-strand	123-135	13	4
β-strand	147-156	10	6
β-strand	164-168	5	4
α-helix	171-174	4
β-strand	175-176	2	5
β-strand	186-199	14	6
β-strand	204-216	13	6
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	280-306	27
α-helix	459-486	28

Chain C: 13 helices, 20 β-strands

Element	Residues	Length	Sheet
α-helix	13-22	10
β-strand	38-48	11	7
β-strand	49	1	8
β-strand	52-53	2	7
β-strand	58-68	11	7
β-strand	70	1	9
α-helix	72-74	3
β-strand	82-85	4	7
α-helix	87-90	4
β-strand	98-100	3	10
β-strand	103	1	7
β-strand	107-108	2	7
β-strand	112	1	6
β-strand	116-121	6	7
β-strand	125	1	9
β-strand	126-137	12	7
α-helix	142-144	3
β-strand	149-153	5	10
β-strand	156-158	3	10
β-strand	166-170	5	7
α-helix	174-176	3
β-strand	178-180	3	7
β-strand	185	1	8
β-strand	190-203	14	10
β-strand	208-220	13	10
α-helix	223-225	3
α-helix	226-230	5
α-helix	231-245	15
α-helix	251-273	23
α-helix	284-308	25
α-helix	315-316	2
α-helix	386-389	4
α-helix	390-415	26

Chain D: 11 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	26-35	10
α-helix	43	1
α-helix	50	1
β-strand	51-57	7	11
β-strand	59-66	8	11
β-strand	71-83	13	11
α-helix	85-87	3
β-strand	95-98	4	11
α-helix	100-105	6
β-strand	111-113	3	12
β-strand	116-121	6	11
β-strand	125	1	10
β-strand	129-134	6	11
β-strand	138-150	13	11
β-strand	162-165	4	12
β-strand	168-171	4	12
β-strand	179-188	10	11
β-strand	201-214	14	12
β-strand	219-231	13	12
α-helix	234-236	3
α-helix	237-241	5
α-helix	242-256	15
α-helix	262-286	25
α-helix	295-318	24
α-helix	411-431	21

Chain E: 14 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	28	1
α-helix	35	1
β-strand	36-51	16	13
β-strand	56-68	13	13
α-helix	70-72	3
β-strand	81	1	13
α-helix	85-90	6
β-strand	96-98	3	3
β-strand	101-106	6	13
β-strand	114-118	5	13
β-strand	123-135	13	13
α-helix	140-142	3
β-strand	147-156	10	3
β-strand	164-168	5	13
β-strand	175-176	2	13
β-strand	186-200	15	3
β-strand	203-216	14	3
α-helix	218-221	4
α-helix	222-226	5
α-helix	227-236	10
α-helix	237-241	5
α-helix	247-270	24
α-helix	278-279	2
α-helix	280-306	27
α-helix	460-486	27

Chain J: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-6	3	14
β-strand	10-12	3	15
β-strand	18-24	7	14
α-helix	29-31	3
β-strand	34-39	6	15
β-strand	45-52	8	15
β-strand	56-59	4	15
β-strand	67-72	6	14
β-strand	77-82	6	14
α-helix	84-86	3
β-strand	88-97	10	15
β-strand	100-103	5	15
β-strand	104	1	14
β-strand	107-111	5	15

Chain K: 1 helix, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-5	2	16
β-strand	10-12	3	17
β-strand	19-20	2	18
β-strand	23	1	18
β-strand	24-25	2	16
β-strand	33-38	6	17
β-strand	45-48	4	17
β-strand	62-66	5	18
β-strand	71-75	5	18
α-helix	80-82	3
β-strand	85-90	6	17
β-strand	101-104	4	17

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit alpha-3	A	protein	492	Mus musculus	P26049 (AlphaFold model)
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

Sequence of entity 1 (A), FASTA

>8G5F_1 Gamma-aminobutyric acid receptor subunit alpha-3 (chains A)
MIITQMWHFYVTRVVLLLLISILPGTTSQGESRRQEPGDFVKQDIGGLSPKHAPDIPDDS
TDNITIFTRILDRLLDGYDNRLRPGLGDAVTEVKTDIYVTSFGPVSDTDMEYTIDVFFRQ
TWHDERLKFDGPMKILPLNNLLASKIWTPDTFFHNGKKSVAHNMTTPNKLLRLVDNGTLL
YTMRLTIHAECPMHLEDFPMDVHACPLKFGSYAYTKAEVIYSWTLGKNKSVEVAQDGSRL
NQYDLLGHVVGTEIIRSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLN
RESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVN
YFTKRSWAWEGKKVPEALEMKKKTPAAPTKKNTTFNIVGTTYPINLAKDTEFSTISKSAA
APSASSTPTAIASPKATYVQDSPAETKTYNSVSKVDKISRIIFPVLFAIFNLVYWATYVN
RESAIKGMIRKQ

Sequence of entity 2 (B, E), FASTA

>8G5F_2 Gamma-aminobutyric acid receptor subunit beta-2 (chains B, E)
MWRVRKRGYFGIWSFPLIIAAVCAQSVNDPSNMSLVKETVDRLLKGYDIRLRPDFGGPPV
AVGMNIDIASIDMVSEVNMDYTLTMYFQQAWRDKRLSYNVIPLNLTLDNRVADQLWVPDT
YFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIES
YGYTTDDIEFYWRGDDNAVTGVTKIELPQFSIVDYKLITKKVVFSTGSYPRLSLSFKLKR
NIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIP
YVKAIDMYLMGCFVFVFMALLEYALVNYIFFGRGPQRQKKAAEKAANANNEKMRLDVNKM
FYKDIKQNGTQYRSLWDPTGDLSPTRRTTNYDFSLYTMDPHENILLSTLEIKNEMATSEA
VMGLGDPRSTMLAYDASSIQYRKAGLPRHSFGRNALERHVAQKKSRLRRRASQLKITIPD
LTDVNAIDRWSRIFFPVVFSFFNIVYWLYYVN

Sequence of entity 3 (C), FASTA

>8G5F_3 Gamma-aminobutyric acid receptor subunit alpha-1 (chains C)
MKKSRGLSDYLWAWTLILSTLSGRSYGQPSQDELKDNTTVFTRILDRLLDGYDNRLRPGL
GERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKI
WTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACP
LKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMT
THFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISAR
NSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDPL
IKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKIDR
LSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 4 (D), FASTA

>8G5F_4 Gamma-aminobutyric acid receptor subunit gamma-2 (chains D)
MSSPNTWSIGSSVYSPVFSQKMTLWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTPKV
PEGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTW
YDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYT
LRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFS
FVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAV
PARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVS
NRKPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKD
CASFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYL

Sequence of entity 5 (J), FASTA

>8G5F_5 Heavy Chain of 8E3 Fab (chains J)
EIQLQQSGPELVKPGTSVKVSCKASGYSFTDYNMYWVKQSHGKSLEWIGYIDPYNADTTY
NREFKGKATLTVDKSSSTAFMHLNSLTSEDSAVYYCARKRNNFYFDYWGQGTPLTVSSAK
TTPPSVYPLAPGCGDTTGSSVTLGCLVKGYFPESVTVTWNSGSLSSSVHTFPALLQSGLY
TMSSSVTVPSSTWPSQTVTCSVAHPASSTTVDKKSAALEVLFQ

Sequence of entity 6 (K), FASTA

>8G5F_6 Light Chain of 8E3 Fab (chains K)
YIVMTQSPKSMSMSLGERVTLSCRASEYVGSYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFAGSGSATDFTLTITSVQAEDLADYHCGQTYNYPTFGGGTKLEIKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Ligands and cofactors

ID	Name	Formula	Copies
Y4B	allopregnanolone	C21 H34 O2	2
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 P26049 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8G4X 2.56 Å, Native GABA-A receptor from the mouse brain, meta-alpha1-alpha3-beta2-gamma2 subtype, in…
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…

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