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Microsecond Dynamics During the Binding-induced Folding of an Intrinsically Disordered Protein

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dc.contributor.author SEN, SREEMANTEE en_US
dc.contributor.author KUMAR, HARISH en_US
dc.contributor.author UDGAONKAR, JAYANT B. en_US
dc.date.accessioned 2021-11-01T04:14:20Z
dc.date.available 2021-11-01T04:14:20Z
dc.date.issued 2021-11 en_US
dc.identifier.citation Journal of Molecular Biology, 433(22), 167254. en_US
dc.identifier.issn 0022-2836 en_US
dc.identifier.uri http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6358
dc.identifier.uri https://doi.org/10.1016/j.jmb.2021.167254 en_US
dc.description.abstract Tau is an intrinsically disordered protein implicated in many neurodegenerative diseases. The repeat domain fragment of tau, tau-K18, is known to undergo a disorder to order transition in the presence of lipid micelles and vesicles, in which helices form in each of the repeat domains. Here, the mechanism of helical structure formation, induced by a phospholipid mimetic, sodium dodecyl sulfate (SDS) at sub-micellar concentrations, has been studied using multiple biophysical probes. A study of the conformational dynamics of the disordered state, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS) has indicated the presence of an intermediate state, I, in equilibrium with the unfolded state, U. The cooperative binding of the ligand (L), SDS, to I has been shown to induce the formation of a compact, helical intermediate (IL5) within the dead time (∼37 µs) of a continuous flow mixer. Quantitative analysis of the PET-FCS data and the ensemble microsecond kinetic data, suggests that the mechanism of induction of helical structure can be described by a U ↔ I ↔ IL5 ↔ FL5 mechanism, in which the final helical state, FL5, forms from IL5 with a time constant of 50–200 µs. Finally, it has been shown that the helical conformation is an aggregation-competent state that can directly form amyloid fibrils. en_US
dc.language.iso en en_US
dc.publisher Elsevier B.V. en_US
dc.subject Biology en_US
dc.subject 2021-OCT-WEEK3 en_US
dc.subject TOC-OCT-2021 en_US
dc.subject 2021 en_US
dc.title Microsecond Dynamics During the Binding-induced Folding of an Intrinsically Disordered Protein en_US
dc.type Article en_US
dc.contributor.department Dept. of Biology en_US
dc.identifier.sourcetitle Journal of Molecular Biology en_US
dc.publication.originofpublisher Foreign en_US


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