7QN8: Human full-length beta3delta GABA(A)R

Cryo-EM structure of human full-length beta3delta GABA(A)R in complex with histamine and nanobody Nb25. Determined by electron microscopy at 3.1 Å resolution. Released 13 Apr 2022.

Method: Electron microscopy
Resolution: 3.1 Å
Organism: Homo sapiens
Chains: 8
Atoms: 16,755
Mol. weight: 315.08 kDa
Ligands: HSM, NAG
Released: 13 Apr 2022

Explore 7QN8 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7QN8 contains 69 α-helices and 98 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.

Chains A, 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	1
β-strand	56-68	13	1
α-helix	70-72	3
β-strand	82-83	2	1
α-helix	85-90	6
β-strand	96-98	3	2
β-strand	101-106	6	1
β-strand	110	1	3
β-strand	114-118	5	1
β-strand	123-135	13	1
β-strand	147-156	10	2
β-strand	164-168	5	1
α-helix	171-173	3
β-strand	175-176	2	1
α-helix	178-180	3
β-strand	186-199	14	2
β-strand	204-216	13	2
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-241	15
α-helix	247-270	24
α-helix	278-279	2
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	82-83	2	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	186-199	14	7
β-strand	204-216	13	7
α-helix	219-221	3
α-helix	222-226	5
α-helix	227-241	15
α-helix	247-270	24
α-helix	278-279	2
α-helix	280-306	27
α-helix	423-446	24

Chain E: 11 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	45-48	4
α-helix	63	1
β-strand	64-79	16	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	200-203	4
α-helix	206-208	3
β-strand	214-224	11	10
β-strand	236-245	10	10
α-helix	249-267	19
α-helix	268-270	3
α-helix	276-299	24
α-helix	309-335	27
α-helix	425-450	26

Chains K, L and M: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	2-7	6	11
β-strand	11	1	12
β-strand	404-413	10	11
β-strand	420-426	7	13
α-helix	431-432	2
β-strand	433-439	7	13
β-strand	445-447	3	13
β-strand	455-460	6	11
β-strand	465-471	7	11
β-strand	479-486	8	13
α-helix	496-498	3
β-strand	499-502	4	13
β-strand	506-508	3	13
β-strand	509	1	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gamma-aminobutyric acid receptor subunit beta-3	A, 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	K, L, M	protein	121	Homo sapiens

Sequence of entity 1 (A, B, C, D), FASTA

>7QN8_1 Gamma-aminobutyric acid receptor subunit beta-3 (chains A, B, C, D)
MWGLAGGRLFGIFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRLRPDFGGPP
VCVGMNIDIASIDMVSEVNMDYTLTMYFQQYWRDKRLAYSGIPLNLTLDNRVADQLWVPD
TYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIE
SYGYTTDDIEFYWRGGDKAVTGVERIELPQFSIVEHRLVSRNVVFATGAYPRLSLSFRLK
RNIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKI
PYVKAIDMYLMGCFVFVFLALLEYAFVNYIFFGRGPQRQKKLAEKTAKAKNDRSKSESNR
VDAHGNILLTSLEVHNEMNEVSGGIGDTRNSAISFDNSGIQYRKQSMPREGHGRFLGDRS
LPHKKTHLRRRSSQLKIKIPDLTDVNAIDRWSRIVFPFTFSLFNLVYWLYYVN

Sequence of entity 2 (E), FASTA

>7QN8_2 Gamma-aminobutyric acid receptor subunit delta (chains E)
MDAPARLLAPLLLLCAQQLRGTRAMNDIGDYVGSNLEISWLPNLDGLIAGYARNFRPGIG
GPPVNVALALEVASIDHISEANMEYTMTVFLHQSWRDSRLSYNHTNETLGLDSRFVDKLW
LPDTFIVNAKSAWFHDVTVENKLIRLQPDGVILYSIRITSTVACDMDLAKYPMDEQECML
DLESYGYSSEDIVYYWSESQEHIHGLDKLQLAQFTITSYRFTTELMNFKSAGQFPRLSLH
FHLRRNRGVYIIQSYMPSVLLVAMSWVSFWISQAAVPARVSLGITTVLTMTTLMVSARSS
LPRASAIKALDVYFWICYVFVFAALVEYAFAHFNADYRKKQKAKVKVSRPRAEMDVRNAI
VLFSLSAAGVTQELAISRRQRRVPGNLMGSYRSVGVETGETKKEGAARSGGQGGIRARLR
PIDADTIDIYARAVFPAAFAAVNVIYWAAYAMGGSGGSGGSGKTETSQVAPA

Sequence of entity 3 (K, L, M), FASTA

>7QN8_3 Nanobody Nb25 (chains K, L, M)
QVQLVESGGGLVQGSLRLSCAASGHTFNYPIMGWFRQAPGKEREFVGAISWSGGSTSYAD
SVKDRFTISRDNAKNTVYLEMNNLKPEDTAVYYCAAKGRYSGGLYYPTNYDYWGQGTQVT
V

Ligands and cofactors

ID	Name	Formula	Copies
HSM	Histamine	C5 H9 N3	3
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	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 P28472 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7A5V 1.7 Å, CryoEM structure of a human gamma-aminobutyric acid receptor, the GABA(A)R-beta3…
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…
6QFA 2.49 Å, CryoEM structure of a beta3K279T GABA(A)R homomer in complex with histamine and megabody…
7QN5 2.5 Å, Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in…
9FAS 2.5 Å, CryoEM structure of human full-length alpha1beta3gamma2L GABA(A)R in complex with…
9FEU 2.5 Å, Cryo-EM structure of the beta3 homomeric GABA(A) receptor in complex with HSM in the…
9FFU 2.5 Å, Cryo-EM structure of the alpha1beta3 GABA(A) receptor in complex with GABA and Mb25 in…
9G2E 2.5 Å, Cryo-EM structure of the beta3 homomeric GABA(A) receptor in the long-lived desensitised…
9QJS 2.52 Å, GABA-A receptor a2b3 (1:4) + a2NB16(silent) + b3Mb125 + GABA
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…

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