dc.contributor.author | Moore, Christopher L. | |
dc.contributor.author | Huang, Michael H. | |
dc.contributor.author | Robbennolt, Shauna A. | |
dc.contributor.author | Voss, Kellen R. | |
dc.contributor.author | Combs, Benjamin | |
dc.contributor.author | Gamblin, Truman Chris | |
dc.contributor.author | Goux, Warren J. | |
dc.date.accessioned | 2017-04-14T20:38:19Z | |
dc.date.available | 2017-04-14T20:38:19Z | |
dc.date.issued | 2011-12-20 | |
dc.identifier.citation | Moore, C. L., Huang, M. H., Robbennolt, S. A., Voss, K. R., Combs, B., Gamblin, T. C., & Goux, W. J. (2011). Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation. Biochemistry, 50(50), 10876–10886. http://doi.org/10.1021/bi2014745 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23712 | |
dc.description.abstract | Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)nZ, Z(X)nZ (n≥2) or (XZ)n (n≥2), where X is a hydrophobic residue and Z is a charged or polar residue. N-acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed 7 peptides, in addition to well known primary nucleating sequences c275VQIINK (AcPHF6*) and Ac306VQIVYK (AcPHF6), formed fibers, tubes, ribbons or rolled sheets. Of the peptides shown by TEM to form amyloid, Ac10VME, AcPHF6*, Ac375KLTFR, and Ac393VYK were found to enhance the fraction of β-structure of AcPHF6 formed at equilibrium, and Ac375KLTFR was found to inhibit AcPHF6 and AcPHF6* aggregation kinetics in a dose-dependent manner, consistent with its participation in a hybrid steric zipper model. Single site mutants were generated which transformed predicted amyloidogenic sequences in tau into non-amyloidogenic ones. A M11K mutant had fewer filaments and showed a decrease in aggregation kinetics and an increased lag time compared to wild type tau, while a F378K mutant showed significantly more filaments. Our results infer that sequences throughout tau, in addition to PHF6 and PHF6*, can seed amyloid formation or affect aggregation kinetics or thermodynamics. | en_US |
dc.publisher | ACS | en_US |
dc.rights | Copyright © 2011 American Chemical Society | en_US |
dc.title | Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Voss, Benjamin | |
kusw.kuauthor | Gamblin, Truman Chris | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1021/bi2014745 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-3136-7545 | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | |