Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Differential assembly diversifies GABA receptor structures and signalling.
Journal, issue, pages	Nature, Vol. 604, Issue 7904, Page 190-194, Year 2022
Publish date	Mar 30, 2022
Authors	Andrija Sente / Rooma Desai / Katerina Naydenova / Tomas Malinauskas / Youssef Jounaidi / Jonas Miehling / Xiaojuan Zhou / Simonas Masiulis / Steven W Hardwick / Dimitri Y Chirgadze / Keith W Miller / A Radu Aricescu /
PubMed Abstract	Type A γ-aminobutyric acid receptors (GABARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits and can be modulated by essential medicines ...Type A γ-aminobutyric acid receptors (GABARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits and can be modulated by essential medicines including general anaesthetics and benzodiazepines. Human GABAR subunits are encoded by 19 paralogous genes that can, in theory, give rise to 495,235 receptor types. However, the principles that govern the formation of pentamers, the permutational landscape of receptors that may emerge from a subunit set and the effect that this has on GABAergic signalling remain largely unknown. Here we use cryogenic electron microscopy to determine the structures of extrasynaptic GABARs assembled from α4, β3 and δ subunits, and their counterparts incorporating γ2 instead of δ subunits. In each case, we identified two receptor subtypes with distinct stoichiometries and arrangements, all four differing from those previously observed for synaptic, α1-containing receptors. This, in turn, affects receptor responses to physiological and synthetic modulators by creating or eliminating ligand-binding sites at subunit interfaces. We provide structural and functional evidence that selected GABAR arrangements can act as coincidence detectors, simultaneously responding to two neurotransmitters: GABA and histamine. Using assembly simulations and single-cell RNA sequencing data, we calculated the upper bounds for receptor diversity in recombinant systems and in vivo. We propose that differential assembly is a pervasive mechanism for regulating the physiology and pharmacology of GABARs.
External links	Nature / PubMed:35355020 / PubMed Central
Methods	EM (single particle)
Resolution	2.5 - 3.4 Å
Structure data	14067 7qn5 EMDB-14067, PDB-7qn5: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with nanobody Nb25 Method: EM (single particle) / Resolution: 2.5 Å 14068 7qn6 EMDB-14068, PDB-7qn6: Cryo-EM structure of human full-length beta3delta GABA(A)R in complex with nanobody Nb25 Method: EM (single particle) / Resolution: 2.9 Å 14069 7qn7 EMDB-14069, PDB-7qn7: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with GABA, histamine and nanobody Nb25 Method: EM (single particle) / Resolution: 3.0 Å 14070 7qn8 EMDB-14070, PDB-7qn8: Cryo-EM structure of human full-length beta3delta GABA(A)R in complex with histamine and nanobody Nb25 Method: EM (single particle) / Resolution: 3.1 Å 14071 7qn9 EMDB-14071, PDB-7qn9: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with GABA, histamine and nanobody Nb25 in a pre-open/closed state Method: EM (single particle) / Resolution: 2.9 Å 14072 7qna EMDB-14072, PDB-7qna: Cryo-EM structure of human full-length alpha4beta3gamma2 GABA(A)R in complex with GABA and nanobody Nb25 Method: EM (single particle) / Resolution: 3.0 Å 14073 7qnb EMDB-14073, PDB-7qnb: Cryo-EM structure of human full-length beta3gamma2 GABA(A)R in complex with GABA and nanobody Nb25 Method: EM (single particle) / Resolution: 3.1 Å 14074 7qnc EMDB-14074, PDB-7qnc: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with THIP (gaboxadol), histamine and nanobody Nb25 Method: EM (single particle) / Resolution: 2.9 Å 14075 7qnd EMDB-14075, PDB-7qnd: Cryo-EM structure of human full-length extrasynaptic beta3delta GABA(A)R in complex with THIP (gaboxadol), histamine and nanobody Nb25 Method: EM (single particle) / Resolution: 3.4 Å 14076 7qne EMDB-14076, PDB-7qne: Cryo-EM structure of human full-length synaptic alpha1beta3gamma2 GABA(A)R in complex with Ro15-4513 and megabody Mb38 Method: EM (single particle) / Resolution: 2.7 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-PX6: 1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE ChemComp-D10: DECANE / Decane ChemComp-OCT: N-OCTANE / Octane ChemComp-EPE: 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / pH bufferYM / HEPES ChemComp-CL: Unknown entry / Chloride ChemComp-HOH: WATER / Water ChemComp-ABU: GAMMA-AMINO-BUTANOIC ACID / neurotransmitter, inhibitorYM / Γ-Aminobutyric acid ChemComp-R16: HEXADECANE / Hexadecane ChemComp-HSM: HISTAMINE / neurotransmitter, hormoneYM / Histamine ChemComp-EI7: 4,5,6,7-tetrahydro-[1,2]oxazolo[5,4-c]pyridin-3-one / alkaloidYM / Gaboxadol ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate ChemComp-EIE: ethyl 8-[(azanylidene-$l^{4}-azanylidene)amino]-5-methyl-6-oxidanylidene-4~{H}-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate / antagonist*YM / Ro15-4513
Source	homo sapiens (human) lama glama (llama)
Keywords	MEMBRANE PROTEIN / pentameric ligand-gated ion channel / neurotransmitter receptor / GABA receptor