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	Modulation of GluA2-γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 30, Issue 10, Page 1481-1494, Year 2023
掲載日	2023年8月31日
著者	Shanti Pal Gangwar / Laura Y Yen / Maria V Yelshanskaya / Aryeh Korman / Drew R Jones / Alexander I Sobolevsky /
PubMed 要旨	Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat ...Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron microscopy structures of rat GluA2 AMPAR complexes with inhibitory mouse γ5 and potentiating human cornichon-2 (CNIH2) auxiliary subunits. CNIH2 appears to destabilize the desensitized state of the complex by reducing the separation of the upper lobes in ligand-binding domain dimers. At the same time, CNIH2 stabilizes binding of polyamine spermidine to the selectivity filter of the closed ion channel. Nevertheless, CNIH2, and to a lesser extent γ5, attenuate polyamine block of the open channel and reduce the potency of the antiepileptic drug perampanel that inhibits the synaptic complex allosterically by binding to sites in the ion channel extracellular collar. These findings illustrate the fine-tuning of synaptic complex structure and function in an auxiliary subunit-dependent manner, which is critical for the study of brain region-specific neurotransmission and design of therapeutics for disease treatment.
リンク	Nat Struct Mol Biol / PubMed:37653241 / PubMed Central
手法	EM (単粒子)
解像度	2.72 - 3.88 Å
構造データ	16052 8bhf EMDB-16052, PDB-8bhf: Cryo-EM structure of stalled rabbit 80S ribosomes in complex with human CCR4-NOT and CNOT4 手法: EM (単粒子) / 解像度: 3.1 Å 40741 8ss2 EMDB-40741, PDB-8ss2: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK and channel blocker spermidine (closed state) 手法: EM (単粒子) / 解像度: 3.58 Å 40742 8ss3 EMDB-40742, PDB-8ss3: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK and channel blocker spermidine (closed state) 手法: EM (単粒子) / 解像度: 3.21 Å 40743 8ss4 EMDB-40743, PDB-8ss4: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunits TARP gamma-5 and cornichon-2 (apo state) 手法: EM (単粒子) / 解像度: 3.3 Å 40744 8ss5 EMDB-40744, PDB-8ss5: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunit TARP gamma-5 (apo state) 手法: EM (単粒子) / 解像度: 3.56 Å 40745 8ss6 EMDB-40745, PDB-8ss6: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK, channel blocker spermidine and antiepileptic drug perampanel (closed state) 手法: EM (単粒子) / 解像度: 3.01 Å 40746 8ss7 EMDB-40746, PDB-8ss7: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK, channel blocker spermidine and antiepileptic drug perampanel (closed state) 手法: EM (単粒子) / 解像度: 2.76 Å 40747 8ss8 EMDB-40747, PDB-8ss8: Structure of AMPA receptor GluA2 complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) 手法: EM (単粒子) / 解像度: 2.81 Å 40748 8ss9 EMDB-40748, PDB-8ss9: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) 手法: EM (単粒子) / 解像度: 2.72 Å 40749 8ssa EMDB-40749, PDB-8ssa: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to glutamate and channel blocker spermidine (desensitized state) 手法: EM (単粒子) / 解像度: 3.88 Å 40750 8ssb EMDB-40750, PDB-8ssb: Structure of LBD-TMD of AMPA receptor GluA2 in complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to glutamate and channel blocker spermidine (desensitized state) 手法: EM (単粒子) / 解像度: 3.66 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-ZN: Unknown entry ChemComp-ZK1: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid / ZK-200775 / アンタゴニスト, 薬剤YM ChemComp-PCW: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / O-(1-O,2-O-ジオレオイル-L-グリセロ-3-ホスホ)コリン / DOPC, リン脂質YM ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-AJP: Digitonin / ジギトニン / 可溶化剤YM ChemComp-SPD: SPERMIDINE / スペルミジン ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-6ZP: 2-(6'-oxo-1'-phenyl[1',6'-dihydro[2,3'-bipyridine]]-5'-yl)benzonitrile / ペランパネル / 薬剤YM ChemComp-HOH: WATER ChemComp-GLU: GLUTAMIC ACID / グルタミン酸
由来	oryctolagus cuniculus (ウサギ) homo sapiens (ヒト) rattus norvegicus (ドブネズミ)
キーワード	RIBOSOME / translational control / mRNA decay / deadenylation / ribosome stalling / human CCR4-NOT / MEMBRANE PROTEIN / AMPA receptor / spermidine / TARP gamma-5 / cornichon-2 / SIGNALING PROTEIN / neurotransmission / Ion-channel / perampanel