7QN7: Gamma-aminobutyric acid receptor subunit alpha-4

Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with GABA, histamine and nanobody Nb25. Determined by electron microscopy at 3.0 Å resolution. Released 13 Apr 2022.

Method: Electron microscopy
Resolution: 3.0 Å
Organism: Homo sapiens
Chains: 7
Atoms: 15,918
Mol. weight: 311.6 kDa
Ligands: NAG, D10, PX6, HSM
Released: 13 Apr 2022

Explore 7QN7 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7QN7 contains 69 α-helices and 85 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: 15 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	49-56	8
α-helix	71	1
β-strand	72-87	16	1
β-strand	92-104	13	1
α-helix	106-108	3
β-strand	116-119	4	1
α-helix	123-126	4
β-strand	132-134	3	2
β-strand	137-142	6	1
β-strand	150-155	6	1
β-strand	159-171	13	1
α-helix	176-178	3
β-strand	183-192	10	2
β-strand	200-204	5	1
α-helix	208-211	4
β-strand	212-213	2	1
α-helix	216-218	3
β-strand	219	1	1
β-strand	224-237	14	2
β-strand	242-254	13	2
α-helix	257-259	3
α-helix	260-264	5
α-helix	265-279	15
α-helix	285-309	25
α-helix	311-312	2
α-helix	316-317	2
α-helix	318-348	31
α-helix	517-543	27

Chains B and C: 13 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	81-83	3	3
α-helix	85-90	6
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
β-strand	147-156	10	4
β-strand	164-168	5	3
α-helix	171-173	3
β-strand	175-176	2	3
α-helix	178-180	3
β-strand	186-200	15	4
β-strand	203-216	14	4
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-241	4
α-helix	247-269	23
α-helix	280-306	27
α-helix	423-446	24

Chain D: 13 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	9-20	12
α-helix	35	1
β-strand	36-51	16	8
β-strand	56-68	13	8
α-helix	70-72	3
β-strand	81-83	3	8
α-helix	85-90	6
β-strand	96-98	3	7
β-strand	101-106	6	8
β-strand	114-118	5	8
β-strand	123-135	13	8
β-strand	147-156	10	7
β-strand	164-168	5	8
α-helix	171-173	3
β-strand	175-176	2	8
α-helix	178-180	3
β-strand	186-200	15	7
β-strand	203-216	14	7
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-237	11
α-helix	238-241	4
α-helix	247-269	23
α-helix	280-306	27
α-helix	423-446	24

Chain E: 9 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	43-48	6
α-helix	63	1
β-strand	64-69	6	9
β-strand	72-79	8	9
β-strand	84-96	13	9
α-helix	98-100	3
β-strand	109-111	3	9
α-helix	113-118	6
β-strand	124-126	3	10
β-strand	129-134	6	9
β-strand	142-146	5	9
β-strand	151-163	13	9
β-strand	175-184	10	10
β-strand	192-196	5	9
α-helix	198-201	4
β-strand	214-224	11	10
β-strand	236-245	10	10
α-helix	249-270	22
α-helix	276-299	24
α-helix	309-334	26
α-helix	425-449	25

Chains F and G: 3 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	2-7	6	11
β-strand	10-11	2	12
β-strand	405-413	9	11
β-strand	420-426	7	12
α-helix	431	1
β-strand	432-439	8	12
β-strand	445-447	3	12
α-helix	449-451	3
β-strand	455-460	6	11
β-strand	465-470	6	11
β-strand	479-486	8	12
α-helix	496-498	3
β-strand	499-502	4	12
β-strand	506-509	4	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit alpha-4	A	protein	554	Homo sapiens	P48169 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit beta-3	B, C, D	protein	473	Homo sapiens	P28472 (AlphaFold model)
Gamma-aminobutyric acid receptor subunit delta	E	protein	472	Homo sapiens	O14764 (AlphaFold model)
Nanobody Nb25	F, G	protein	121	Homo sapiens

Sequence of entity 1 (A), FASTA

>7QN7_1 Gamma-aminobutyric acid receptor subunit alpha-4 (chains A)
MVSAKKVPAIALSAGVSFALLRFLCLAVCLNESPGQNQKEEKLCTENFTRILDSLLDGYD
NRLRPGFGGPVTEVKTDIYVTSFGPVSDVEMEYTMDVFFRQTWIDKRLKYDGPIEILRLN
NMMVTKVWTPDTFFRNGKKSVSHNMTAPNKLFRIMRNGTILYTMRLTISAECPMRLVDFP
MDGHACPLKFGSYAYPKSEMIYTWTKGPEKSVEVPKESSSLVQYDLIGQTVSSETIKSIT
GEYIVMTVYFHLRRKMGYFMIQTYIPCIMTVILSQVSFWINKESVPARTVFGITTVLTMT
TLSISARHSLPKVSYATAMDWFIAVCFAFVFSALIEFAAVNYFTNIQMEKAKRKTSKPPQ
EVPAAPVQREKHPEAPLQNTNANLNMRKRTNALVHSESDVGNRTEVGNHSSKSSTVVQES
SKGTPRSYLASSPNPFSRANAAETISAARALPSASPTSIRTGYMPRKASVGSASTRHVFG
SRLQRIKTTVNTIGATGKLSATPPPSAPPPSGSGTSKIDKYARILFPVTFGAFNMVYWVV
YLSKDTMEKSESLM

Sequence of entity 2 (B, C, D), FASTA

>7QN7_2 Gamma-aminobutyric acid receptor subunit beta-3 (chains B, C, D)
MWGLAGGRLFGIFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRLRPDFGGPP
VCVGMNIDIASIDMVSEVNMDYTLTMYFQQYWRDKRLAYSGIPLNLTLDNRVADQLWVPD
TYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIE
SYGYTTDDIEFYWRGGDKAVTGVERIELPQFSIVEHRLVSRNVVFATGAYPRLSLSFRLK
RNIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKI
PYVKAIDMYLMGCFVFVFLALLEYAFVNYIFFGRGPQRQKKLAEKTAKAKNDRSKSESNR
VDAHGNILLTSLEVHNEMNEVSGGIGDTRNSAISFDNSGIQYRKQSMPREGHGRFLGDRS
LPHKKTHLRRRSSQLKIKIPDLTDVNAIDRWSRIVFPFTFSLFNLVYWLYYVN

Sequence of entity 3 (E), FASTA

>7QN7_3 Gamma-aminobutyric acid receptor subunit delta (chains E)
MDAPARLLAPLLLLCAQQLRGTRAMNDIGDYVGSNLEISWLPNLDGLIAGYARNFRPGIG
GPPVNVALALEVASIDHISEANMEYTMTVFLHQSWRDSRLSYNHTNETLGLDSRFVDKLW
LPDTFIVNAKSAWFHDVTVENKLIRLQPDGVILYSIRITSTVACDMDLAKYPMDEQECML
DLESYGYSSEDIVYYWSESQEHIHGLDKLQLAQFTITSYRFTTELMNFKSAGQFPRLSLH
FHLRRNRGVYIIQSYMPSVLLVAMSWVSFWISQAAVPARVSLGITTVLTMTTLMVSARSS
LPRASAIKALDVYFWICYVFVFAALVEYAFAHFNADYRKKQKAKVKVSRPRAEMDVRNAI
VLFSLSAAGVTQELAISRRQRRVPGNLMGSYRSVGVETGETKKEGAARSGGQGGIRARLR
PIDADTIDIYARAVFPAAFAAVNVIYWAAYAMGGSGGSGGSGKTETSQVAPA

Sequence of entity 4 (F, G), FASTA

>7QN7_4 Nanobody Nb25 (chains F, G)
QVQLVESGGGLVQGSLRLSCAASGHTFNYPIMGWFRQAPGKEREFVGAISWSGGSTSYAD
SVKDRFTISRDNAKNTVYLEMNNLKPEDTAVYYCAAKGRYSGGLYYPTNYDYWGQGTQVT
V

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	6
D10	Decane	C10 H22	4
PX6	1,2-dipalmitoyl-sn-glycero-3-phosphate	C35 H68 O8 P	1
HSM	Histamine	C5 H9 N3	2
R16	Hexadecane	C16 H34	2
ABU	Gamma-amino-butanoic acid	C4 H9 N O2	1

Primary citation

Differential assembly diversifies GABA A receptor structures and signalling. Sente, A., Desai, R., Naydenova, K. et al. Nature (2022) 604:190-194. DOI 10.1038/s41586-022-04517-3 · PubMed

Other PDB entries of the same protein (UniProt P48169 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7QN5 2.5 Å, Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in…
9SL1 2.68 Å, GABA-A a4b3d receptor in complex with GABA, Nb24 and Mb30
7QN9 2.9 Å, Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in…
7QNC 2.9 Å, Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in…
7QNA 3.0 Å, Cryo-EM structure of human full-length alpha4beta3gamma2 GABA(A)R in complex with GABA…
9SLD 3.04 Å, GABA-A a4b3d receptor in complex with DS2-Me, GABA, Nb24 and Mb30

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