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  Structural impact of Tau phosphorylation at threonine 231.

Schwalbe, M., Kadavath, H., Biernat, J., Ozenne, V., Blackledge, M., Mandelkow, E., et al. (2015). Structural impact of Tau phosphorylation at threonine 231. Structure, 23(8), 1448-1458. doi:10.1016/j.str.2015.06.002.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-29AA-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-FAA9-3
Genre: Journal Article

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Schwalbe, M.1, Author              
Kadavath, H.1, Author              
Biernat, J., Author
Ozenne, V., Author
Blackledge, M., Author
Mandelkow, E., Author
Zweckstetter, M.1, Author              
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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 Abstract: Phosphorylation of the microtubule-associated protein Tau influences the assembly and stabilization of microtubules and is deregulated in several neurodegenerative diseases. The high flexibility of Tau, however, has prevented an atomic-level description of its phosphorylation-induced structural changes. Employing an extensive set of distance and orientational restraints together with a novel ensemble calculation approach, we determined conformational ensembles of Tau fragments in the non-phosphorylated state and, when phosphorylated at T231/S235 or T231/S235/S237/S238, four important sites of phosphorylation in Alzheimer disease. Comparison of the molecular ensembles showed that phosphorylation of the regulatory T231 does not perturb the backbone conformation of the proximal microtubule-binding 225KVAVVR230 motif. Instead, phosphorylated T231 selectively engages in a salt bridge with R230 that can compete with the formation of intermolecular salt bridges to tubulin. Our study provides an ensemble description which will be useful for the analysis of conformational transitions in Tau and other intrinsically disordered proteins.

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Language(s): eng - English
 Dates: 2015-07-092015-08-04
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.str.2015.06.002
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Title: Structure
Source Genre: Journal
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Pages: - Volume / Issue: 23 (8) Sequence Number: - Start / End Page: 1448 - 1458 Identifier: -