6BB4

Fab/epitope complex of mouse monoclonal antibody C5.2 targeting a phospho-tau epitope.

6BB4 の概要

• エントリーDOI: 10.2210/pdb6bb4/pdb
• 分子名称: Mouse monoclonal antibody C5.2 Fab light chain, Mouse monoclonal antibody C5.2 Fab heavy chain, Microtubule-associated protein tau, ... (5 entities in total)
• 機能のキーワード: monoclonal antibody, fab, tau, phosphorylation state -specific antibody, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 150081.75

構造登録者

Chukwu, J.E.,Kong, X.-P. (登録日: 2017-10-16, 公開日: 2018-05-02, 最終更新日: 2024-10-30)

主引用文献

Chukwu, J.E.,Pedersen, J.T.,Pedersen, L.O.,Volbracht, C.,Sigurdsson, E.M.,Kong, X.P.
Tau Antibody Structure Reveals a Molecular Switch Defining a Pathological Conformation of the Tau Protein.
Sci Rep, 8:6209-6209, 2018

PubMed Abstract: Tau antibodies have shown therapeutic potential for Alzheimer's disease and several are in clinical trials. As a microtubule-associated protein, tau relies on dynamic phosphorylation for its normal functions. In tauopathies, it becomes hyperphosphorylated and aggregates into toxic assemblies, which collectively lead to neurodegeneration. Of the phospho-epitopes, the region around Ser396 has received particular attention because of its prominence and stability in tauopathies. Here we report the first structure of a monoclonal tau antibody in complex with the pathologically important phospho-Ser396 residue. Its binding region reveals tau residues Tyr394 to phospho-Ser396 stabilized in a β-strand conformation that is coordinated by a phospho-specific antigen binding site. These details highlight a molecular switch that defines this prominent conformation of tau and ways to target it. Overall, the structure of the antibody-antigen complex clarifies why certain phosphorylation sites in tau are more closely linked to neurodegeneration than others.

PubMed: 29670132
DOI: 10.1038/s41598-018-24276-4

実験手法

X-RAY DIFFRACTION (2.099 Å)