Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6317
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dc.contributor.authorBhate, Suhas H.en_US
dc.contributor.authorUDGAONKAR, JAYANT B.en_US
dc.contributor.authorDas, Ranabiren_US
dc.date.accessioned2021-10-18T10:30:51Z
dc.date.available2021-10-18T10:30:51Z
dc.date.issued2021-11en_US
dc.identifier.citationProtein Science, 30(11), 2258-2271.en_US
dc.identifier.issn0961-8368en_US
dc.identifier.issn1469-896Xen_US
dc.identifier.urihttp://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6317
dc.identifier.urihttps://doi.org/10.1002/pro.4188en_US
dc.description.abstractThe prion protein (PrP) misfolds and oligomerizes at pH 4 in the presence of physiological salt concentrations. Low pH and salt cause structural perturbations in the monomeric prion protein that lead to misfolding and oligomerization. However, the changes in stability within different regions of the PrP prior to oligomerization are poorly understood. In this study, we have characterized the local stability in PrP at high resolution using amide temperature coefficients (TC) measured by nuclear magnetic resonance (NMR) spectroscopy. The local stability of PrP was investigated under native as well as oligomerizing conditions. We have also studied the rapidly oligomerizing PrP variant (Q216R) and the protective PrP variant (A6). We report that at low pH, salt destabilizes PrP at several polar residues, and the hydrogen bonds in helices α2 and α3 are weakened. In addition, salt changes the curvature of the α3 helix, which likely disrupts α2–α3 contacts and leads to oligomerization. These results are corroborated by the TC values of rapidly oligomerizing Q216R-PrP. The poly-alanine substitution in A6-PrP stabilizes α2, which prevents oligomerization. Altogether, these results highlight the importance of native polar interactions in determining the stability of PrP and reveal the structural disruptions in PrP that lead to misfolding and oligomerization.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.subjectNMRen_US
dc.subjectPolar interactionsen_US
dc.subjectPrion proteinen_US
dc.subjectProtein misfoldingen_US
dc.subjectprotein oligomerizationen_US
dc.subjectTemperature coefficientsen_US
dc.subject2021-OCT-WEEK1en_US
dc.subjectTOC-OCT-2021en_US
dc.subject2021en_US
dc.titleDestabilization of polar interactions in the prion protein triggers misfolding and oligomerizationen_US
dc.typeArticleen_US
dc.contributor.departmentDept. of Biologyen_US
dc.identifier.sourcetitleProtein Scienceen_US
dc.publication.originofpublisherForeignen_US
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