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dc.contributor.authorEschmann, Neil A.
dc.contributor.authorGeorgieva, Elka R.
dc.contributor.authorGanguly, Pritam
dc.contributor.authorBorbat, Peter P.
dc.contributor.authorRappaport, Maxime D.
dc.contributor.authorAkdoğan, Yaşar
dc.contributor.authorFreed, Jack H.
dc.contributor.authorShea, Joan-Emma
dc.contributor.authorHan, Songi
dc.date.accessioned2017-10-16T11:27:22Z
dc.date.available2017-10-16T11:27:22Z
dc.date.issued2017-03
dc.identifier.citationEschmann, N. A., Georgieva, E. R., Ganguly, P., Borbat, P. P., Rappaport, M. D., Akdoğan, Y., Freed, J. H., Shea, J.-E., and Han, S. (2017). Signature of an aggregation-prone conformation of tau. Scientific Reports, 7. doi:10.1038/srep44739en_US
dc.identifier.issn2045-2322
dc.identifier.urihttp://doi.org/10.1038/srep44739
dc.identifier.urihttp://hdl.handle.net/11147/6362
dc.description.abstractThe self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6∗, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6 (∗) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages of aggregation, well before fibril formation. Combined with simulations, our experiments show that the extended β-strand conformational state of PHF6 (∗) is readily populated under aggregating conditions, constituting a defining signature of aggregation-prone tau, and as such, a possible target for therapeutic interventions.en_US
dc.description.sponsorshipNIH (S10 RR028992); NIH Innovator award; NIH/NIGMS (R21EB022731-- P41-GM103521), NSF (MCB 1158577); NSF MRSEC Program (DMR 1121053); Center for Scientific Computing at the UCSB CNSI (CNS-0960316); Extreme Science and Engineering Discovery Environment-XSEDE - NSF (TG-MCA05S027--ACI-1053575); University of California; Santa Barbara; University of California, Office of the Presidenten_US
dc.language.isoengen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionof10.1038/srep44739en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectTau proteinen_US
dc.subjectIntrinsically disordered proteinen_US
dc.subjectNeurofibrillary tanglesen_US
dc.subjectAggregationen_US
dc.titleSignature of an aggregation-prone conformation of tauen_US
dc.typearticleen_US
dc.contributor.authorIDTR180857en_US
dc.contributor.institutionauthorAkdoğan, Yaşar
dc.relation.journalScientific Reportsen_US
dc.contributor.departmentIzmir Institute of Technology. Materials Science and Engineeringen_US
dc.identifier.volume7en_US
dc.identifier.wosWOS:000396647000001
dc.identifier.scopusSCOPUS:2-s2.0-85015721684
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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