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-Structure paper
| タイトル | Molecular mechanism of calcium permeability and magnesium block in NMDA receptors. |
|---|---|
| ジャーナル・号・ページ | Nat Neurosci, Vol. 29, Issue 6, Page 1293-1302, Year 2026 |
| 掲載日 | 2026年5月5日 |
著者 | Ruben Steigerwald / Max Epstein / Tsung-Han Chou / Noriko Simorowski / Hiro Furukawa / ![]() |
| PubMed 要旨 | Hebbian neuroplasticity, which is thought to be a cellular substrate of learning and memory, can occur by means of coincidental detection of presynaptic neurotransmitter release and Ca influx upon ...Hebbian neuroplasticity, which is thought to be a cellular substrate of learning and memory, can occur by means of coincidental detection of presynaptic neurotransmitter release and Ca influx upon postsynaptic depolarization. This is mediated at a molecular level by N-methyl-D-aspartate-type glutamate receptors, which bind glutamate and glycine and facilitate Ca influx upon relief of Mg channel block during membrane depolarization. However, the structural mechanism underlying Ca permeability and Mg blockade in N-methyl-D-aspartate-type glutamate receptors has yet to be fully elucidated. Here we demonstrate using single-particle cryo-electron microscopy that Ca permeation through the narrow constriction of the cation selectivity filter involves partial dehydration, as evidenced by several Ca binding sites. In contrast, Mg binds outside of the selectivity filter through a water network and remains hydrated, thereby acting as a channel blocker. Furthermore, the lipid network around the selectivity filter influences the stability of Mg binding in a voltage-dependent manner. Our study details the transmembrane chemistry essential for initiating neuroplasticity. |
リンク | Nat Neurosci / PubMed:42086762 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.59 - 3.6 Å |
| 構造データ | EMDB-70297, PDB-9obs: EMDB-70298, PDB-9obt: EMDB-70299, PDB-9obu: EMDB-70300, PDB-9obv: EMDB-70301, PDB-9obw: EMDB-70302, PDB-9obx: EMDB-70303, PDB-9oby: EMDB-70304, PDB-9obz: EMDB-70305, PDB-9oc0: EMDB-70306, PDB-9oc1: EMDB-70307, PDB-9oc2: |
| 化合物 | ![]() ChemComp-GLY: ![]() ChemComp-GLU: ![]() ChemComp-CLR: ![]() ChemComp-POV: ![]() ChemComp-HOH: ![]() ChemComp-MG: ![]() ChemComp-CA: |
| 由来 |
|
キーワード | MEMBRANE PROTEIN / Ion Channels / NMDAR / membrane proteins / ion channel |
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