EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Architecture, dynamics and biogenesis of GluA3 AMPA glutamate receptors.
ジャーナル・号・ページ	Nature, Vol. 645, Issue 8080, Page 535-543, Year 2025
掲載日	2025年7月1日
著者	Aditya Pokharna / Imogen Stockwell / Josip Ivica / Bishal Singh / Johannes Schwab / Carlos Vega-Gutiérrez / Beatriz Herguedas / Ondrej Cais / James M Krieger / Ingo H Greger /
PubMed 要旨	AMPA-type glutamate receptors (AMPARs) mediate the majority of excitatory neurotransmission in the brain. Assembled from combinations of four core subunits, GluA1-4 and around 20 auxiliary subunits, ...AMPA-type glutamate receptors (AMPARs) mediate the majority of excitatory neurotransmission in the brain. Assembled from combinations of four core subunits, GluA1-4 and around 20 auxiliary subunits, their molecular diversity tunes information transfer and storage in a brain-circuit-specific manner. GluA3, a subtype strongly associated with disease, functions as both a fast-transmitting Ca-permeable AMPAR at sensory synapses, and as a Ca-impermeable receptor at cortical synapses. Here we present cryo-electron microscopy structures of the Ca-permeable GluA3 homomer, which substantially diverges from other AMPARs. The GluA3 extracellular domain tiers (N-terminal domain (NTD) and ligand-binding domain (LBD)) are closely coupled throughout gating states, creating interfaces that impact signalling and contain human disease-associated mutations. Central to this architecture is a stacking interaction between two arginine residues (Arg163) in the NTD dimer interface, trapping a unique NTD dimer conformation that enables close contacts with the LBD. Rupture of the Arg163 stack not only alters the structure and dynamics of the GluA3 extracellular region, but also increases receptor trafficking and the expression of GluA3 heteromers at the synapse. We further show that a mammalian-specific GluA3 trafficking checkpoint determines the conformational stability of the LBD tier. Thus, specific design features define communication and biogenesis of GluA3, offering a framework to examine this disease-associated glutamate receptor.
リンク	Nature / PubMed:40592473 / PubMed Central
手法	EM (単粒子)
解像度	2.59 - 3.77 Å
構造データ	52325 9hpc EMDB-52325, PDB-9hpc: The TMD and the LBD region of the AMPAR complex GluA3- TARP gamma2 in the apo state. 手法: EM (単粒子) / 解像度: 2.59 Å 52326 9hpd EMDB-52326, PDB-9hpd: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the open state. 手法: EM (単粒子) / 解像度: 2.96 Å 52327 9hpe EMDB-52327: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the apo state. PDB-9hpe: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the apo state 手法: EM (単粒子) / 解像度: 2.9 Å 52328 9hpf EMDB-52328, PDB-9hpf: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the desensitised state. 手法: EM (単粒子) / 解像度: 3.77 Å 52329 9hpg EMDB-52329, PDB-9hpg: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3(R439G,R163I)- TARP gamma2 in the apo state. 手法: EM (単粒子) / 解像度: 3.35 Å 52332 9hpk EMDB-52332, PDB-9hpk: Open state TMD-LBD of the GluA3(R439G) with TARP gamma2 手法: EM (単粒子) / 解像度: 2.59 Å 53109 9qfh EMDB-53109, PDB-9qfh: The composite map of of the AMPAR complex GluA3- TARP gamma2 in the apo state. 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-HOH: WATER
由来	Rattus (ネズミ) rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmission / ion channel / glutamate