9FAM: Human full-length alpha1beta3gamma2 GABA(A)R

CryoEM structure of human full-length alpha1beta3gamma2 GABA(A)R in complex with GARLH4, the TMD of Neuroligin2, GABA and Megabody38 in a desensitised state (StateD3). Determined by electron microscopy at 3.5 Å resolution. Released 2 Jul 2025.

Method: Electron microscopy
Resolution: 3.5 Å
Organisms: Homo sapiens, Lama glama
Chains: 8
Atoms: 17,822
Mol. weight: 337.78 kDa
Ligands: PIO, ABU, HEX, D10
Released: 2 Jul 2025

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

Secondary structure: helices and β-sheets

9FAM contains 77 α-helices and 87 β-strands across 8 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: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	13-23	11
β-strand	39-54	16	1
β-strand	59-71	13	1
α-helix	73-75	3
β-strand	84-86	3	1
α-helix	88-93	6
β-strand	99-101	3	2
β-strand	104	1	1
β-strand	108-109	2	1
β-strand	117-121	5	1
β-strand	126-138	13	1
α-helix	143-145	3
β-strand	150-159	10	2
β-strand	167-171	5	1
β-strand	179-181	3	1
β-strand	186	1	1
β-strand	191-204	14	2
β-strand	209-221	13	2
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-242	11
α-helix	243-246	4
α-helix	252-271	20
α-helix	285-309	25
α-helix	387-390	4
α-helix	391-416	26

Chain B: 14 helices, 13 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	1	3
α-helix	87-90	4
β-strand	96-98	3	4
β-strand	101-106	6	3
β-strand	110	1	5
β-strand	114-118	5	3
β-strand	123-135	13	3
α-helix	140-142	3
β-strand	147-156	10	4
β-strand	164-168	5	3
α-helix	171-174	4
β-strand	175-176	2	3
β-strand	186-200	15	4
β-strand	203-216	14	4
α-helix	217	1
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-235	9
α-helix	238-241	4
α-helix	247-268	22
α-helix	280-316	37
α-helix	420-446	27

Chain C: 12 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	26-35	10
α-helix	43	1
β-strand	51-66	16	10
β-strand	71-83	13	10
α-helix	85-87	3
β-strand	95-98	4	10
α-helix	100-102	3
β-strand	111-113	3	5
β-strand	116-121	6	10
β-strand	125	1	7
β-strand	129-134	6	10
β-strand	138-150	13	10
β-strand	162-171	10	5
β-strand	179-190	12	10
β-strand	201-214	14	5
β-strand	219-231	13	5
α-helix	234-236	3
α-helix	237-241	5
α-helix	242-256	15
α-helix	262-283	22
α-helix	295-318	24
α-helix	319-323	5
α-helix	375-379	5
α-helix	402-426	25

Chain D: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	13-23	11
β-strand	39-54	16	6
β-strand	59-71	13	6
α-helix	73-75	3
β-strand	83-86	4	6
α-helix	90-93	4
β-strand	99-101	3	7
β-strand	104	1	6
β-strand	108-109	2	6
β-strand	117-122	6	6
β-strand	126-138	13	6
β-strand	150-159	10	7
β-strand	167-171	5	6
β-strand	179-181	3	6
β-strand	186	1	6
β-strand	191-204	14	7
β-strand	209-221	13	7
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	274-276	3
α-helix	285-310	26
α-helix	387-390	4
α-helix	391-416	26

Chain E: 15 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	35	1
β-strand	36-46	11	8
β-strand	50-51	2	8
β-strand	56-68	13	8
α-helix	70-72	3
β-strand	81-83	3	8
α-helix	85-89	5
β-strand	96-98	3	9
β-strand	101-106	6	8
β-strand	114-118	5	8
β-strand	123-135	13	8
β-strand	147-156	10	9
β-strand	164-168	5	8
α-helix	171-173	3
β-strand	176	1	8
α-helix	178-180	3
β-strand	186-199	14	9
β-strand	204-216	13	9
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-236	10
α-helix	238-241	4
α-helix	247-269	23
α-helix	280-303	24
α-helix	304-308	5
α-helix	310-316	7
α-helix	420-446	27

Chain G: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	14
β-strand	11-12	2	15
β-strand	423-431	9	14
β-strand	439-445	7	2
β-strand	452-457	6	2
β-strand	462-465	4	2
α-helix	467-469	3
β-strand	474-478	5	14
β-strand	483-489	7	14
α-helix	493-495	3
β-strand	497-504	8	2
α-helix	513-515	3
β-strand	518-519	2	2
β-strand	523-525	3	2
β-strand	526-527	2	15

Chain H: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	674-698	25

Chain L: 8 helices, 9 β-strands

Element	Residues	Length	Sheet
α-helix	12-42	31
β-strand	47-48	2	11
β-strand	58-59	2	11
β-strand	64-66	3	11
β-strand	76-78	3	11
β-strand	80	1	12
β-strand	83	1	12
α-helix	84-86	3
α-helix	90-112	23
α-helix	113-117	5
α-helix	121-145	25
α-helix	146-151	6
α-helix	153-159	7
β-strand	164	1	13
β-strand	167	1	13
β-strand	172-173	2	11
α-helix	175-202	28

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit alpha-1	A, D	protein	413	Homo sapiens	P14867 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit beta-3	B, E	protein	441	Homo sapiens	P28472 (AlphaFold model)
Isoform 2 of Gamma-aminobutyric acid receptor subunit gamma-2	C	protein	405	Homo sapiens	P18507 (AlphaFold model)
Neuroligin-2	H	protein	33	Homo sapiens	Q8NFZ4 (AlphaFold model)
LHFPL tetraspan subfamily member 4 protein	L	protein	193	Homo sapiens	Q7Z7J7
Megabody38	G	protein	539	Lama glama

Sequence of entity 1 (A, D), FASTA

>9FAM_1 Gamma-aminobutyric acid receptor subunit alpha-1 (chains A, D)
DNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQS
WKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLY
TMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLN
QYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNR
ESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNY
FTKRGYAWDGKSVVPEKPKKVKDPLIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIE
PKEVKPETKPPEPKKTFNSVSKIDRLSRIAFPLLFGIFNLVYWATYLNREPQL

Sequence of entity 2 (B, E), FASTA

>9FAM_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

>9FAM_3 Isoform 2 of Gamma-aminobutyric acid receptor subunit gamma-2 (chains C)
GDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWYD
RRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTLR
LTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSFV
GLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVPA
RTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSNR
KPSKDKDKKKKNPAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKDCASFFCCFED
CRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYLG

Sequence of entity 4 (H), FASTA

>9FAM_4 Neuroligin-2 (chains H)
DSRDYSTELSVTVAVGASLLFLNILAFAALYYK

Sequence of entity 5 (L), FASTA

>9FAM_5 LHFPL tetraspan subfamily member 4 protein (chains L)
YHEHYMRNSRAIGVLWAIFTICFAIINVVVFIQPYWVGDSVSTPKPGYFGLFHYCVGSGL
AGRELTCRGSFTDFSTIPSSAFKAAAFFVLLSMVLILGCITCFSLFFFCNTATVYKICAW
MQLLAALCLVLGCMIFPDGWDAETIRDMCGAKTGKYSLGDCSVRWAYILAIIGILNALIL
SFLAFVLGNRQTD

Sequence of entity 6 (G), FASTA

>9FAM_6 Megabody38 (chains G)
QVQLQESGGGLVQTKTTTSVIDTTNDAQNLLTQAQTIVNTLKDYCPILIAKSSSSNGGTN
NANTPSWQTAGGGKNSCATFGAEFSAASDMINNAQKIVQETQQLSANQPKNITQPHNLNL
NSPSSLTALAQKMLKNAQSQAEILKLANQVESDFNKLSSGHLKDYIGKCDASAISSANMT
MQNQKNNWGNGCAGVEETQSLLKTSAADFNNQTPQINQAQNLANTLIQELGNNPFRASGG
GSGGGGSGKLSDTYEQLSRLLTNDNGTNSKTSAQAINQAVNNLNERAKTLAGGTTNSPAY
QATLLALRSVLGLWNSMGYAVICGGYTKSPGENNQKDFHYTDENGNGTTINCGGSTNSNG
THSYNGTNTLKADKNVSLSIEQYEKIHEAYQILSKALKQAGLAPLNSKGEKLEAHVTTSK
YGSLRVSCAASGRTFTTYIMAWFRQAPGKEREFLAAMDQGRIQYYGDSVRGRFTISRDYA
KNSVDLQLDGLRPEDTAVYYCAAGAGFWGLRTASSYHYWGQGTQVTVSSHHHHHHEPEA

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
ABU	Gamma-amino-butanoic acid	C4 H9 N O2	2
HEX	Hexane	C6 H14	7
D10	Decane	C10 H22	1
PLM	Palmitic acid	C16 H32 O2	1
CLR	Cholesterol	C27 H46 O	1
PGW	(1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexade…	C40 H77 O10 P	2

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

Primary citation

CryoEM structure of human full-length alpha1beta3gamma2 GABA(A)R in complex with GARLH4, the TMD of Neuroligin2, GABA and Megabody in a desensitised state (StateD3). 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…
9FAS 2.5 Å, CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with…
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…

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