9FAS: Human full-length alpha1beta3gamma2L GABA(A)R

CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with pregnenolone sulfate. Determined by electron microscopy at 2.5 Å resolution. Released 28 May 2025.

Method: Electron microscopy
Resolution: 2.5 Å
Organism: Homo sapiens
Chains: 5
Atoms: 15,501
Mol. weight: 259.23 kDa
Ligands: PIO, HEX, NAG, A8W
Released: 28 May 2025

Explore 9FAS in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9FAS contains 66 α-helices and 64 β-strands across 5 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: 14 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	14-22	9
α-helix	38	1
β-strand	39-54	16	1
β-strand	59-71	13	1
α-helix	73-75	3
β-strand	83-86	4	1
α-helix	88-91	4
β-strand	99-101	3	2
β-strand	104	1	1
β-strand	108-109	2	1
β-strand	117-122	6	1
β-strand	126-138	13	1
β-strand	150-159	10	2
β-strand	167-171	5	1
α-helix	175-178	4
β-strand	179-181	3	1
β-strand	186	1	1
β-strand	191-205	15	2
β-strand	208-221	14	2
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-242	11
α-helix	243-246	4
α-helix	252-273	22
α-helix	274-276	3
α-helix	285-309	25
α-helix	387-390	4
α-helix	391-415	25

Chain B: 13 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	35	1
β-strand	36-51	16	3
β-strand	56-68	13	3
α-helix	70-72	3
β-strand	81-83	3	3
α-helix	85-90	6
β-strand	96-98	3	4
β-strand	101-106	6	3
β-strand	114-118	5	3
β-strand	123-135	13	3
β-strand	147-156	10	4
β-strand	164-168	5	3
α-helix	171-173	3
β-strand	175-176	2	3
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	238-241	4
α-helix	247-270	24
α-helix	278-279	2
α-helix	280-316	37
α-helix	420-445	26

Chain C: 14 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	26-35	10
α-helix	50	1
β-strand	51-66	16	5
β-strand	71-83	13	5
α-helix	85-87	3
β-strand	95-98	4	5
α-helix	100-102	3
β-strand	111-113	3	6
β-strand	116-121	6	5
β-strand	129-134	6	5
β-strand	138-150	13	5
β-strand	162-171	10	6
β-strand	179-190	12	5
α-helix	193-195	3
β-strand	201-215	15	6
β-strand	218-231	14	6
α-helix	234-236	3
α-helix	237-241	5
α-helix	242-252	11
α-helix	253-256	4
α-helix	262-283	22
α-helix	295-318	24
α-helix	319-323	5
α-helix	410-430	21
α-helix	431-435	5

Chain D: 11 helices, 14 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	117-122	6	7
β-strand	126-138	13	7
β-strand	150-159	10	8
β-strand	167-171	5	7
β-strand	179-181	3	7
β-strand	186	1	7
β-strand	191-205	15	8
β-strand	208-221	14	8
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	285-309	25
α-helix	387-390	4
α-helix	391-417	27

Chain E: 14 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	35	1
β-strand	36-47	12	9
β-strand	51	1	9
β-strand	56-68	13	9
α-helix	70-72	3
β-strand	81-83	3	9
α-helix	85-90	6
β-strand	96-98	3	10
β-strand	101-106	6	9
β-strand	114-118	5	9
β-strand	123-135	13	9
β-strand	147-156	10	10
β-strand	164-168	5	9
α-helix	171-173	3
β-strand	175-176	2	9
β-strand	186-201	16	10
β-strand	203-216	14	10
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-241	4
α-helix	247-268	22
α-helix	269-271	3
α-helix	278-279	2
α-helix	280-316	37
α-helix	420-446	27

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit alpha-1	A, D	protein	409	Homo sapiens	P14867 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit beta-3	B, E	protein	441	Homo sapiens	P28472 (AlphaFold model)
Isoform 1 of Gamma-aminobutyric acid receptor subunit gamma-2	C	protein	412	Homo sapiens	P18507 (AlphaFold model)

Sequence of entity 1 (A, D), FASTA

>9FAS_1 Gamma-aminobutyric acid receptor subunit alpha-1 (chains A, D)
DNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQS
WKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLY
TMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLN
QYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNR
ESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNY
FTKRGYAWDGKSVVPEKPKKVKDPLIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIE
PKEVKPETKPPEPKKTFNSVSKIDRLSRIAFPLLFGIFNLVYWATYLNR

Sequence of entity 2 (B, E), FASTA

>9FAS_2 Gamma-aminobutyric acid receptor subunit beta-3 (chains B, E)
GNMSFVKETVDKLLKGYDIRLRPDFGGPPVCVGMNIDIASIDMVSEVNMDYTLTMYFQQY
WRDKRLAYSGIPLNLTLDNRVADQLWVPDTYFLNDKKSFVHGVTVKNRMIRLHPDGTVLY
GLRITTTAACMMDLRRYPLDEQNCTLEIESYGYTTDDIEFYWRGGDKAVTGVERIELPQF
SIVEHRLVSRNVVFATGAYPRLSLSFRLKRNIGYFILQTYMPSILITILSWVSFWINYDA
SAARVALGITTVLTMTTINTHLRETLPKIPYVKAIDMYLMGCFVFVFLALLEYAFVNYIF
FGRGPQRQKKLAEKTAKAKNDRSKSESNRVDAHGNILLTSLEVHNEMNEVSGGIGDTRNS
AISFDNSGIQYRKQSMPREGHGRFLGDRSLPHKKTHLRRRSSQLKIKIPDLTDVNAIDRW
SRIVFPFTFSLFNLVYWLYYV

Sequence of entity 3 (C), FASTA

>9FAS_3 Isoform 1 of Gamma-aminobutyric acid receptor subunit gamma-2 (chains C)
GDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWYD
RRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTLR
LTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSFV
GLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVPA
RTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSNR
KPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKDCA
SFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYL

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
HEX	Hexane	C6 H14	8
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1
A8W	Pregnenolone sulfate	C21 H32 O5 S	1
R16	Hexadecane	C16 H34	5
PX2	1,2-dilauroyl-sn-glycero-3-phosphate	C27 H52 O8 P	1
PLM	Palmitic acid	C16 H32 O2	3
D10	Decane	C10 H22	17
PGW	(1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexade…	C40 H77 O10 P	3

Water and common crystallization additives (CL) are not listed.

Primary citation

CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with pregnenolone sulfate. Kasaragod, V.B., Aricescu, A.R. To be published.

Other PDB entries of the same protein (UniProt P14867 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9RGD 2.0 Å, CryoEM structure of human alpha1beta3gamma2L GABA(A)R in CL47a
9EQG 2.4 Å, CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with GABA…
9FFU 2.5 Å, Cryo-EM structure of the alpha1beta3 GABA(A) receptor in complex with GABA and Mb25 in…
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
8PET 2.6 Å, Cryo-EM structure of the full-length human alpha1beta3 GABA(A) receptor (babba…
9FAJ 2.6 Å, CryoEM structure of human full-length alpha1beta3gamma2 GABA(A) receptor in complex with…
9FAK 2.6 Å, CryoEM structure of human full-length alpha1beta3gamma2 GABA(A) receptor in complex with…
9FGG 2.6 Å, Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in Saposin A…
8SGO 2.65 Å, Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus pregnenolone…
7QNE 2.7 Å, Cryo-EM structure of human full-length synaptic alpha1beta3gamma2 GABA(A)R in complex…
9FG7 2.7 Å, Cryo-EM structure of the full-length alpha1beta3gamma2 GABA(A) receptor in complex with…

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