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Hyperphosphorylation of tau induces local structural changes
Author(s) -
Bielska Agata Agnieszka,
Zondlo Neal J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a63-b
Subject(s) - hyperphosphorylation , chemistry , neuroscience , microbiology and biotechnology , biology , phosphorylation
Protein phosphorylation is a ubiquitous regulatory and signaling mechanism used throughout the cell. We have analyzed the conformational effects of serine‐threonine phosphorylation in proline‐rich peptides whose sequences were derived from the protein tau. Tau is a member of the microtubule‐associated‐proteins (MAPs) and binds microtubules in neurons to stabilize their elongated structure in the axon. In Alzheimer’s disease and other tauopathies, tau becomes hyperphosphorylated. This is thought to cause a conformational change resulting in the dissociation of tau from microtubules and aggregation into neurofibrillary tangles (NFTs). We have observed significant conformational changes upon tau phosphorylation by circular dichroism spectroscopy (CD), fluorescence resonance energy transfer (FRET), and NMR. A common phosphorylation‐induced structural change in the proline‐rich peptides favored a type two polyproline helix (PPII) secondary structure. Funding for this work was provided by HHMI and UDRF