6BB4
Fab/epitope complex of mouse monoclonal antibody C5.2 targeting a phospho-tau epitope.
Summary for 6BB4
| Entry DOI | 10.2210/pdb6bb4/pdb |
| Descriptor | Mouse monoclonal antibody C5.2 Fab light chain, Mouse monoclonal antibody C5.2 Fab heavy chain, Microtubule-associated protein tau, ... (5 entities in total) |
| Functional Keywords | monoclonal antibody, fab, tau, phosphorylation state -specific antibody, immune system |
| Biological source | Mus musculus More |
| Total number of polymer chains | 9 |
| Total formula weight | 150081.75 |
| Authors | Chukwu, J.E.,Kong, X.-P. (deposition date: 2017-10-16, release date: 2018-05-02, Last modification date: 2024-10-30) |
| Primary citation | 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 Cited by 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: 29670132DOI: 10.1038/s41598-018-24276-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.099 Å) |
Structure validation
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