5J7J

NMR Derived Structure of Ca2+ Calmodulin bound to Phosphorylated PSD-95

5J7J の概要

• エントリーDOI: 10.2210/pdb5j7j/pdb
• 関連するPDBエントリー: 2MES
• NMR情報: BMRB: 30062
• 分子名称: Calmodulin, Disks large homolog 4, CALCIUM ION (3 entities in total)
• 機能のキーワード: phosphorylated, calmodulin, psd-95, voltage-gated channel, metal binding protein
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19290.30

構造登録者

Turner, M.L.,Ames, J.B.,Anderson, D.E. (登録日: 2016-04-06, 公開日: 2017-10-25, 最終更新日: 2024-11-06)

主引用文献

Chowdhury, D.,Turner, M.,Patriarchi, T.,Hergarden, A.C.,Anderson, D.,Zhang, Y.,Sun, J.,Chen, C.Y.,Ames, J.B.,Hell, J.W.
Ca2+/calmodulin binding to PSD-95 mediates homeostatic synaptic scaling down.
Embo J., 37:122-138, 2018

PubMed Abstract: Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca influx, Ca/calmodulin (Ca/CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca/CaM by interacting with R126 on CaM. Mutating E17 to R prevented homeostatic scaling down in primary hippocampal neurons, which is rescued via charge inversion by ectopic expression of CaM, as determined by analysis of miniature excitatory postsynaptic currents. Accordingly, increased binding of Ca/CaM to PSD-95 induced by a chronic increase in Ca influx is a critical molecular event in homeostatic downscaling of glutamatergic synaptic transmission.

PubMed: 29118000
DOI: 10.15252/embj.201695829

実験手法

SOLUTION NMR