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dc.contributor.authorLyons, Albert
dc.contributor.authorGandhi, Neha
dc.contributor.authorMancera, Ricardo
dc.date.accessioned2017-01-30T14:03:31Z
dc.date.available2017-01-30T14:03:31Z
dc.date.created2015-01-28T20:00:42Z
dc.date.issued2014
dc.identifier.citationLyons, A. and Gandhi, N. and Mancera, R. 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.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/37474
dc.description.abstract

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 ß-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.

dc.publisherWiley
dc.relation.urihttp://onlinelibrary.wiley.com/doi/10.1002/prot.24544/abstract
dc.subjecttau protein
dc.subjectmicrotubule
dc.subjectMAPT
dc.subjectmolecular dynamics
dc.subjectphosphorylation
dc.titleMolecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragment
dc.typeJournal Article
dcterms.source.volume82
dcterms.source.startPage1907
dcterms.source.endPage1923
dcterms.source.issn10970134
dcterms.source.titleProteins: Function, Structure, and Bioinformatics
curtin.note

This is the accepted version of the following article: "Lyons, A. and Gandhi, N. and Mancera, R. 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.", which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/prot.24544/abstract

curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access


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