6X3S: Human GABAA receptor alpha1-beta2-gamma2 subtype

Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with bicuculline methbromide. Determined by electron microscopy at 3.12 Å resolution. Released 9 Sept 2020.

Method: Electron microscopy
Resolution: 3.12 Å
Organisms: Homo sapiens, Mus musculus
Chains: 9
Atoms: 17,407
Mol. weight: 364.82 kDa
Ligands: NAG, MAN, J94
Released: 9 Sept 2020

Explore 6X3S in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6X3S contains 55 α-helices and 115 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, 12 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	35	1
β-strand	36-51	16	1
β-strand	56-68	13	1
β-strand	81-83	3	1
α-helix	85-89	5
β-strand	96-97	2	2
β-strand	101-106	6	1
β-strand	114-118	5	1
β-strand	123-135	13	1
β-strand	147-156	10	2
β-strand	164-168	5	1
β-strand	175-176	2	1
β-strand	188-200	13	2
β-strand	203-215	13	2
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-240	3
α-helix	247-271	25
α-helix	280-305	26
α-helix	310-338	29

Chain B: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	11-22	12
β-strand	39-54	16	3
β-strand	59-71	13	3
α-helix	73-75	3
β-strand	83-86	4	3
α-helix	87	1
α-helix	88-91	4
β-strand	99-101	3	4
β-strand	104	1	3
β-strand	108-109	2	3
β-strand	117-122	6	3
β-strand	126-138	13	3
β-strand	150-159	10	4
β-strand	167-171	5	3
α-helix	175-177	3
β-strand	179-181	3	3
β-strand	186	1	3
β-strand	193-205	13	4
β-strand	208-220	13	4
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-243	12
α-helix	244-246	3
α-helix	252-273	22
α-helix	285-310	26
α-helix	315-345	31

Chain C: 11 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	35	1
β-strand	36-51	16	5
β-strand	56-68	13	5
β-strand	81-83	3	5
α-helix	85-89	5
β-strand	96-98	3	6
β-strand	101-106	6	5
β-strand	114-118	5	5
β-strand	123-135	13	5
β-strand	147-156	10	6
β-strand	164-168	5	5
β-strand	175-176	2	5
β-strand	188-199	12	6
β-strand	204-215	12	6
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	247-271	25
α-helix	280-304	25
α-helix	310-338	29

Chain D: 11 helices, 15 β-strands

Element	Residues	Length	Sheet
α-helix	13-22	10
β-strand	39-54	16	7
β-strand	59-71	13	7
α-helix	73-75	3
β-strand	83-86	4	7
α-helix	88-91	4
β-strand	99-101	3	8
β-strand	104	1	7
β-strand	108-109	2	7
β-strand	113	1	6
β-strand	117-122	6	7
β-strand	126-138	13	7
β-strand	150-159	10	8
β-strand	167-171	5	7
α-helix	175-177	3
β-strand	179-181	3	7
β-strand	186	1	7
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	252-276	25
α-helix	285-310	26
α-helix	315-345	31

Chain E: 10 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	26-34	9
α-helix	50	1
β-strand	51-56	6	9
β-strand	59-66	8	9
β-strand	71-83	13	9
β-strand	95-98	4	9
α-helix	100-105	6
β-strand	111-113	3	10
β-strand	116-121	6	9
β-strand	125	1	8
β-strand	130-134	5	9
β-strand	138-150	13	9
β-strand	162-171	10	10
β-strand	179-183	5	9
β-strand	190	1	9
β-strand	201-214	14	10
β-strand	219-231	13	10
α-helix	235-236	2
α-helix	237-241	5
α-helix	242-251	10
α-helix	253-256	4
α-helix	262-285	24
α-helix	295-323	29
α-helix	325-353	29

Chain I: 0 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	11
β-strand	10-12	3	12
β-strand	19-25	7	11
β-strand	33-38	6	13
β-strand	45-48	4	13
β-strand	54	1	13
β-strand	62-65	4	11
β-strand	70-75	6	11
β-strand	85-90	6	13
β-strand	96-97	2	13
β-strand	101	1	13
β-strand	102-104	3	12

Chain J: 1 helix, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	14
β-strand	10-12	3	15
β-strand	17-25	9	14
α-helix	29-31	3
β-strand	34-39	6	15
β-strand	45-51	7	15
β-strand	58-60	3	15
β-strand	68-73	6	14
β-strand	78-84	7	14
β-strand	92-98	7	15
β-strand	107-108	2	15
β-strand	112-116	5	15

Chain K: 0 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	19
β-strand	10-11	2	20
β-strand	18-25	8	19
β-strand	34-39	6	21
β-strand	45-52	8	21
β-strand	57-60	4	21
β-strand	68-73	6	19
β-strand	78-83	6	19
β-strand	93-99	7	21
β-strand	105-108	4	21
β-strand	112-113	2	21
β-strand	114-115	2	20

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 type A 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

>6X3S_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

>6X3S_2 Gamma-aminobutyric acid receptor subunit alpha-1 (chains B, D)
QPSLQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEY
TIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLR
ITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVV
VAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVIL
SQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSA
LIEFATVNYFTKSQPARAAKIDRLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ

Sequence of entity 3 (E), FASTA

>6X3S_3 Gamma-aminobutyric acid type A receptor subunit gamma-2 (chains E)
WSHPQFEKGGGSGGGSGGSSAWSHPQFEKLEVLFQGPQKSDDDYEDYASNKTWVLTPKVP
EGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWY
DRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTL
RLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSF
VGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVP
ARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSS
QPARAAKMDSYARIFFPTAFCLFNLVYWVSYLYLSRGSGATNFSLLKQAGDVEENPG

Sequence of entity 4 (I, L), FASTA

>6X3S_4 Kappa Fab Light Chain (chains I, L)
NIVMTQSPKSMSMSVGERVTLSCKASEYVGTYVSWYQQKPEQSPKLLIYGASNRYTGVPD
RFTGSGSATDFTLTIGSVQAEDLADYHCGQSYSYPTFGAGTKLELKRADAAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 5 (J, K), FASTA

>6X3S_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	3
MAN	alpha-D-mannopyranose	C6 H12 O6	1
J94	(5S)-6,6-dimethyl-5-[(6R)-8-oxo-6,8-dihydrofuro[3,4-e][1,3]benzodioxol-6-yl]-5,…	C21 H20 N O6	2

Primary citation

Shared structural mechanisms of general anaesthetics and benzodiazepines. Kim, J.J., Gharpure, A., Teng, J. et al. Nature (2020) 585:303-308. DOI 10.1038/s41586-020-2654-5 · 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…
8SI9 2.98 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus…

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