Molecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragment

Lyons, Albert J., Gandhi, Neha S., & Mancera, Ricardo L. (2014) Molecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragment. Proteins: Structure, Function and Bioinformatics, 82(9), pp. 1907-1923.

View at publisher


Aggregation of the microtubule associated protein tau (MAPT) within neurons of the brain is the leading cause of tauopathies such as Alzheimer's disease. MAPT is a phospho-protein that is selectively phosphorylated by a number of kinases in vivo to perform its biological function. However, it may become pathogenically hyperphosphorylated, causing aggregation into paired helical filaments and neurofibrillary tangles. The phosphorylation induced conformational change on a peptide of MAPT (htau225−250) was investigated by performing molecular dynamics simulations with different phosphorylation patterns of the peptide (pThr231 and/or pSer235) in different simulation conditions to determine the effect of ionic strength and phosphate charge. All phosphorylation patterns were found to disrupt a nascent terminal β-sheet pattern (226VAVVR230 and 244QTAPVP249), replacing it with a range of structures. The double pThr231/pSer235 phosphorylation pattern at experimental ionic strength resulted in the best agreement with NMR structural characterization, with the observation of a transient α-helix (239AKSRLQT245). PPII helical conformations were only found sporadically throughout the simulations. Proteins 2014; 82:1907–1923. © 2014 Wiley Periodicals, Inc.

Impact and interest:

5 citations in Scopus
Search Google Scholar™
6 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 93839
Item Type: Journal Article
Refereed: Yes
DOI: 10.1002/prot.24544
ISSN: 1097-0134
Divisions: Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 04 Apr 2016 06:28
Last Modified: 14 Apr 2016 03:13

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page