9E4Z
GluA2-gamma2 complex bound glutamate and cyclothiazide
9E4Z の概要
エントリーDOI | 10.2210/pdb9e4z/pdb |
EMDBエントリー | 47521 |
分子名称 | Isoform Flip of Glutamate receptor 2, Voltage-dependent calcium channel gamma-2 subunit, GLUTAMIC ACID, ... (4 entities in total) |
機能のキーワード | ligand-gated ion channel, ionotropic glutamate receptor, ampa receptor, ion channel, transport protein |
由来する生物種 | Rattus norvegicus (Norway rat) 詳細 |
タンパク質・核酸の鎖数 | 8 |
化学式量合計 | 458052.72 |
構造登録者 | Montano Romero, A.,Carrillo, E.,Jayaraman, V.,Twomey, E.C. (登録日: 2024-10-25, 公開日: 2025-06-18, 最終更新日: 2025-07-16) |
主引用文献 | Carrillo, E.,Montano Romero, A.,Gonzalez, C.U.,Turcu, A.L.,Vazquez, S.,Twomey, E.C.,Jayaraman, V. Memantine inhibits calcium-permeable AMPA receptors. Nat Commun, 16:5576-5576, 2025 Cited by PubMed Abstract: Memantine is an US Food and Drug Administration (FDA) approved drug that is thought to selectively inhibit NMDA-subtype of ionotropic glutamate receptors (NMDARs). NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine blocks CP-AMPAR ion channels in a unique mechanism of action from NMDARs. Furthermore, we demonstrate that memantine inhibits a gain of function AMPAR mutation found in a patient with a neurodevelopmental disorder. Our findings unlock potential exploitation of this site to design more specific drugs targeting CP-AMPARs. PubMed: 40593487DOI: 10.1038/s41467-025-60543-5 主引用文献が同じPDBエントリー |
実験手法 | ELECTRON MICROSCOPY (3.7 Å) |
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