Tau Antibody Structure Reveals a Molecular Switch Defining a Pathological Conformation of the Tau Protein
| العنوان: | Tau Antibody Structure Reveals a Molecular Switch Defining a Pathological Conformation of the Tau Protein |
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| المؤلفون: | Einar M. Sigurdsson, Xiang-Peng Kong, Christiane Volbracht, Jessica E. Chukwu, Jan Torleif Pedersen, Lars Østergaard Pedersen |
| المصدر: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Models, Molecular, Protein Conformation, Tau protein, Amino Acid Motifs, lcsh:Medicine, tau Proteins, Plasma protein binding, Article, 03 medical and health sciences, Epitopes, Immunoglobulin Fab Fragments, Structure-Activity Relationship, 0302 clinical medicine, Protein structure, Alzheimer Disease, Antibody Specificity, medicine, Humans, Amino Acid Sequence, Binding site, Phosphorylation, lcsh:Science, Peptide sequence, Multidisciplinary, Binding Sites, biology, Chemistry, Neurodegeneration, lcsh:R, Antibodies, Monoclonal, medicine.disease, Cell biology, 030104 developmental biology, biology.protein, lcsh:Q, Alzheimer's disease, Peptides, 030217 neurology & neurosurgery, Protein Binding |
| الوصف: | 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. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9afc1d8dad00a388972873e35adf75f3 https://pubmed.ncbi.nlm.nih.gov/29670132 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9afc1d8dad00a388972873e35adf75f3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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