6HUG: Human full-length alpha1beta3gamma2L GABA(A)R

CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with picrotoxin and megabody Mb38. Determined by electron microscopy at 3.1 Å resolution. Released 2 Jan 2019.

Method: Electron microscopy
Resolution: 3.1 Å
Organisms: Bos taurus, Homo sapiens, Lama glama
Chains: 6
Atoms: 15,289
Mol. weight: 330.97 kDa
Ligands: PIO, RI5
Released: 2 Jan 2019

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

Secondary structure: helices and β-sheets

6HUG contains 66 α-helices and 77 β-strands across 6 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	11-20	10
β-strand	39-50	12	1
α-helix	52-53	2
β-strand	54	1	1
β-strand	59-71	13	1
α-helix	73-75	3
β-strand	83-85	3	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
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	191-204	14	2
β-strand	209-221	13	2
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-243	12
α-helix	244-246	3
α-helix	252-275	24
α-helix	285-309	25
α-helix	316-318	3
α-helix	387-390	4
α-helix	391-414	24

Chain B: 12 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	85-87	3
β-strand	96-98	3	4
β-strand	101-106	6	3
β-strand	115-118	4	3
β-strand	123-135	13	3
α-helix	140-142	3
β-strand	147-156	10	4
β-strand	164-168	5	3
β-strand	176	1	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	227-235	9
α-helix	238-241	4
α-helix	247-271	25
α-helix	280-307	28
α-helix	420-445	26

Chain C: 12 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	27-34	8
α-helix	43	1
β-strand	51-62	12	5
β-strand	71-83	13	5
α-helix	85-87	3
β-strand	95-98	4	5
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
β-strand	201-214	14	6
β-strand	219-231	13	6
α-helix	232	1
α-helix	237-241	5
α-helix	242-252	11
α-helix	253-256	4
α-helix	262-280	19
α-helix	282-284	3
α-helix	295-318	24
α-helix	319-323	5
α-helix	410-434	25

Chain D: 12 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	10-20	11
α-helix	31	1
β-strand	39-49	11	7
β-strand	53-54	2	7
β-strand	59-71	13	7
α-helix	73-75	3
β-strand	83-85	3	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
α-helix	175-178	4
β-strand	180-181	2	7
β-strand	191-203	13	8
β-strand	210-221	12	8
α-helix	224-226	3
α-helix	227-231	5
α-helix	232-242	11
α-helix	243-246	4
α-helix	252-275	24
α-helix	285-308	24
α-helix	391-414	24

Chain E: 14 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	10-19	10
α-helix	28	1
α-helix	35	1
β-strand	36-51	16	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	176	1	9
β-strand	186-199	14	10
β-strand	204-216	13	10
α-helix	217	1
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-236	10
α-helix	237-240	4
α-helix	247-271	25
α-helix	280-307	28
α-helix	421-445	25

Chain G: 2 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	4	1	11
β-strand	5-6	2	12
β-strand	11-12	2	13
β-strand	424-429	6	12
β-strand	439-446	8	2
β-strand	450-457	8	2
β-strand	462-465	4	2
β-strand	474-478	5	12
β-strand	483-488	6	12
α-helix	493-495	3
β-strand	497-504	8	2
α-helix	513-515	3
β-strand	519	1	2
β-strand	520	1	11
β-strand	524-525	2	2
β-strand	526-527	2	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit alpha-1	A, D	protein	437	Bos taurus	P08219 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit beta-3	B, E	protein	473	Homo sapiens	P28472 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit gamma-2	C	protein	495	Homo sapiens	P18507 (AlphaFold model)
Megabody Mb38	G	protein	539	Lama glama

Sequence of entity 1 (A, D), FASTA

>6HUG_1 Gamma-aminobutyric acid receptor subunit alpha-1 (chains A, D)
DYKDDDDKQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPGLGERVTEVKTDIFVTSFGP
VSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASKIWTPDTFFHNGKKSVAHNM
TMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHACPLKFGSYAYTRAEVVYEWT
REPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVMTTHFHLKRKIGYFVIQTYL
PCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAV
CYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDPLIKKNNTYAPTATSYTPNL
ARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKIDRLSRIAFPLLFGIFNLVYW
ATYLNREPQLKAPTPHQ

Sequence of entity 2 (B, E), FASTA

>6HUG_2 Gamma-aminobutyric acid receptor subunit beta-3 (chains B, E)
MCSGLLELLLPIWLSWTLGTRGSEPRSVNDPGNMSFVKETVDKLLKGYDIRLRPDFGGPP
VCVGMNIDIASIDMVSEVNMDYTLTMYFQQYWRDKRLAYSGIPLNLTLDNRVADQLWVPD
TYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIE
SYGYTTDDIEFYWRGGDKAVTGVERIELPQFSIVEHRLVSRNVVFATGAYPRLSLSFRLK
RNIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKI
PYVKAIDMYLMGCFVFVFLALLEYAFVNYIFFGRGPQRQKKLAEKTAKAKNDRSKSESNR
VDAHGNILLTSLEVHNEMNEVSGGIGDTRNSAISFDNSGIQYRKQSMPREGHGRFLGDRS
LPHKKTHLRRRSSQLKIKIPDLTDVNAIDRWSRIVFPFTFSLFNLVYWLYYVN

Sequence of entity 3 (C), FASTA

>6HUG_3 Gamma-aminobutyric acid receptor subunit gamma-2 (chains C)
MSSPNIWSTGSSVYSTPVFSQKMTVWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTPK
VPEGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQT
WYDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLY
TLRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQF
SFVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDA
VPARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFV
SNRKPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGK
DCASFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYLGGSGG
SGGSGKTETSQVAPA

Sequence of entity 4 (G), FASTA

>6HUG_4 Megabody Mb38 (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
RI5	(1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-2a-hydroxy-8b-methyl-9-(prop-1-en-2-yl)hexahydro…	C15 H16 O6	1

Primary citation

GABAAreceptor signalling mechanisms revealed by structural pharmacology. Masiulis, S., Desai, R., Uchanski, T. et al. Nature (2019) 565:454-459. DOI 10.1038/s41586-018-0832-5 · PubMed

Other PDB entries of the same protein (UniProt P08219 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6HUJ 3.04 Å, CryoEM structure of human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex…
6HUO 3.26 Å, CryoEM structure of human full-length heteromeric alpha1beta3gamma2L GABA(A)R in complex…
6HUP 3.58 Å, CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with…
6HUK 3.69 Å, CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with…

Browse structure collections

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