edoc

Structural impact of proline-directed pseudophosphorylation at AT8, AT100, and PHF1 epitopes on 441-residue tau

Bibow, Stefan and Ozenne, Valéry and Biernat, Jacek and Blackledge, Martin and Mandelkow, Eckhard and Zweckstetter, Markus. (2011) Structural impact of proline-directed pseudophosphorylation at AT8, AT100, and PHF1 epitopes on 441-residue tau. Journal of the American Chemical Society, 133 (40). pp. 15842-15845.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/94078/

Downloads: Statistics Overview

Abstract

The intrinsically disordered protein tau becomes excessively phosphorylated and aggregates into neurofibrillary tangles in Alzheimer's disease. To obtain insight into the structural consequences of phosphorylation, we characterized a mutant protein of tau in which epitopes recognized by Alzheimer diagnostic antibodies were mimicked by mutation to glutamic acid [AT8 (S199E, S202E, T205E), AT100 (T212E and S214E), and PHF1 (S396E and S404E)]. A large number of distance restraints obtained from NMR paramagnetic relaxation enhancement in combination with ensemble conformer calculations demonstrate that pseudophosphorylation causes an opening of the transient folding of tau. Together with previous studies on the Parkinson-related protein α-synuclein, our data indicate that networks of transient long-range interactions are common properties of intrinsically disordered proteins and that their modulation is important for aggregation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
UniBasel Contributors:Bibow, Stefan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:0002-7863
e-ISSN:1520-5126
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Mar 2023 08:11
Deposited On:22 Mar 2023 15:10

Repository Staff Only: item control page