Tau Antibody Structure Reveals a Molecular Switch Defining a Pathological Conformation of the Tau Protein.

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 highli

SUBMITTER: Chukwu JE 

PROVIDER: S-EPMC5906480 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature