National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
CA206573
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS083660
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS107253
米国
National Science Foundation (NSF, United States)
1818086
米国
引用
ジャーナル: Mol Cell / 年: 2021 タイトル: Structure and desensitization of AMPA receptor complexes with type II TARP γ5 and GSG1L. 著者: Oleg Klykov / Shanti Pal Gangwar / Maria V Yelshanskaya / Laura Yen / Alexander I Sobolevsky / 要旨: AMPA receptors (AMPARs) mediate the majority of excitatory neurotransmission. Their surface expression, trafficking, gating, and pharmacology are regulated by auxiliary subunits. Of the two types of ...AMPA receptors (AMPARs) mediate the majority of excitatory neurotransmission. Their surface expression, trafficking, gating, and pharmacology are regulated by auxiliary subunits. Of the two types of TARP auxiliary subunits, type I TARPs assume activating roles, while type II TARPs serve suppressive functions. We present cryo-EM structures of GluA2 AMPAR in complex with type II TARP γ5, which reduces steady-state currents, increases single-channel conductance, and slows recovery from desensitization. Regulation of AMPAR function depends on its ligand-binding domain (LBD) interaction with the γ5 head domain. GluA2-γ5 complex shows maximum stoichiometry of two TARPs per AMPAR tetramer, being different from type I TARPs but reminiscent of the auxiliary subunit GSG1L. Desensitization of both GluA2-GSG1L and GluA2-γ5 complexes is accompanied by rupture of LBD dimer interface, while GluA2-γ5 but not GluA2-GSG1L LBD dimers remain two-fold symmetric. Different structural architectures and desensitization mechanisms of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV 詳細: 1mM Quisqualate was added to the purified protein and incubated on ice for 30 min before sample preparation.
詳細
Protein extracted and reconstituted in detergent micelle
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 1 / 平均露光時間: 2.5 sec. / 平均電子線量: 58.0 e/Å2