4FL5

Crystal structure of human 14-3-3 sigma in complex with a Tau-protein peptide surrounding pS214

4FL5 の概要

• エントリーDOI: 10.2210/pdb4fl5/pdb
• 関連するPDBエントリー: 3LW1 3MHR 3NKX 3P1N
• 分子名称: 14-3-3 protein sigma, Microtubule-associated protein tau, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: peptide binding protein, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P31947; Cytoplasm, cytosol : P10636
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 56069.04

構造登録者

Schumacher, B.,Ottmann, C. (登録日: 2012-06-14, 公開日: 2013-12-11, 最終更新日: 2024-11-27)

主引用文献

Joo, Y.,Schumacher, B.,Landrieu, I.,Bartel, M.,Smet-Nocca, C.,Jang, A.,Choi, H.S.,Jeon, N.L.,Chang, K.A.,Kim, H.S.,Ottmann, C.,Suh, Y.H.
Involvement of 14-3-3 in tubulin instability and impaired axon development is mediated by Tau.
FASEB J., 29:4133-4144, 2015

PubMed Abstract: 14-3-3 proteins act as adapters that exert their function by interacting with their various protein partners. 14-3-3 proteins have been implicated in a variety of human diseases including neurodegenerative diseases. 14-3-3 proteins have recently been reported to be abundant in the neurofibrillary tangles (NFTs) observed inside the neurons of brains affected by Alzheimer's disease (AD). These NFTs are mainly constituted of phosphorylated Tau protein, a microtubule-associated protein known to bind 14-3-3. Despite this indication of 14-3-3 protein involvement in the AD pathogenesis, the role of 14-3-3 in the Tauopathy remains to be clarified. In the present study, we shed light on the role of 14-3-3 proteins in the molecular pathways leading to Tauopathies. Overexpression of the 14-3-3σ isoform resulted in a disruption of the tubulin cytoskeleton and prevented neuritic outgrowth in neurons. NMR studies validated the phosphorylated residues pSer214 and pSer324 in Tau as the 2 primary sites for 14-3-3 binding, with the crystal structure of 14-3-3σ in complex with Tau-pSer214 and Tau-pSer324 revealing the molecular details of the interaction. These data suggest a rationale for a possible pharmacologic intervention of the Tau/14-3-3 interaction.

PubMed: 26103986
DOI: 10.1096/fj.14-265009

実験手法

X-RAY DIFFRACTION (1.9 Å)