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PDBsum entry 6bb4
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Immune system
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PDB id
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6bb4
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References listed in PDB file
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Key reference
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Title
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Tau antibody structure reveals a molecular switch defining a pathological conformation of the tau protein.
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Authors
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J.E.Chukwu,
J.T.Pedersen,
L.Ã.˜.Pedersen,
C.Volbracht,
E.M.Sigurdsson,
X.P.Kong.
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Ref.
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Sci Rep, 2018,
8,
6209.
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PubMed id
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Abstract
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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.
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