Phosphorylation-induced structural reorganization in Tau-paired helical filaments

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dc.contributor.author Rani, Lata
dc.contributor.author Mallajosyula, Sairam S.
dc.coverage.spatial United States of America
dc.date.accessioned 2021-05-14T05:18:44Z
dc.date.available 2021-05-14T05:18:44Z
dc.date.issued 2021-05
dc.identifier.citation Rani, Lata and Mallajosyula, Sairam S., "Phosphorylation-induced structural reorganization in Tau-paired helical filaments", ACS Chemical Neuroscience, DOI: 10.1021/acschemneuro.1c00084, vol. 12, no. 9, pp. 1621-1631, May 2021 en_US
dc.identifier.issn 1948-7193
dc.identifier.uri https://doi.org/10.1021/acschemneuro.1c00084
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/6449
dc.description.abstract Taupathies involve the deposition of abnormal tau protein into neurofibrillary tangles (NFTs) in the human brain. The abnormally hyperphosphorylated tau dissociates from microtubules and forms insoluble aggregates known as paired helical filaments (PHFs), highlighting the importance of post-translational modifications in taupathies. The present study examines the factors responsible for the structural stability of PHFs in native as well as in phosphorylated and O-GlcNAcylated tau. We carried out molecular dynamics simulations on the R3-R4 repeat domains of the human tau protein to gain atomic insights into the key noncovalent interactions responsible for their unique dimeric C-shaped structure. The structural effects upon post-translational modification were found to be prominent for phosphorylation when compared with O-GlcNAcylation. O-GlcNAcylated tau was found to retain the "C conformation" observed in the native tau PHF, whereas upon phosphorylation, we observed a conformational transition to a more opened "H conformation". We found that this conformational transition is brought about by the loss of a key salt bridge between Lys353 and Asp358 due to the phosphorylation at Ser356 that results in the reorganization of the dimeric interface.
dc.description.statementofresponsibility by Lata Rani and Sairam S. Mallajosyula
dc.format.extent vol. 12, no. 9, pp. 1621-1631
dc.language.iso en_US en_US
dc.publisher American Chemical Society en_US
dc.subject Tau en_US
dc.subject paired-helical filaments en_US
dc.subject hyperphosphorylation en_US
dc.subject O-GlcNAcylation en_US
dc.title Phosphorylation-induced structural reorganization in Tau-paired helical filaments en_US
dc.type Article en_US
dc.relation.journal ACS Chemical Neuroscience


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