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dc.contributor.authorZhao, Jing
dc.contributor.authorHuvent, Isabelle
dc.contributor.authorLippens, Guy
dc.contributor.authorEliezer, David
dc.contributor.authorZhang, Anqiang
dc.contributor.authorLi, Quanhong
dc.contributor.authorTessier, Peter
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorZhang, Fuming
dc.contributor.authorWang, Chunyu
dc.identifier.citationGlycan Determinants of Heparin-Tau Interaction, J. Zhao, I. Huvent, G. Lippens, D. Eliezer, A. Zhang, Q. Li, P. M. Tessier, R. J. Linhardt, F. Zhang, and C. Wang, Biophysical Journal, 112, 921–932, 2017.
dc.descriptionBiophysical Journal, 112, 921–932
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractTau aggregates into paired helical filaments within neurons, a pathological hallmark of Alzheimer's disease. Heparin promotes tau aggregation and recently has been shown to be involved in the cellular uptake of tau aggregates. Although the tau-heparin interaction has been extensively studied, little is known about the glycan determinants of this interaction. Here, we used surface plasmon resonance (SPR) and NMR spectroscopy to characterize the interaction between two tau fragments, K18 and K19, and several polysaccharides, including heparin, heparin oligosaccharides, chemically modified heparin, and related glycans. Using a heparin-immobilized chip, SPR revealed that tau K18 and K19 bind heparin with a KD of 0.2 and 70 μM, respectively. In SPR competition experiments, N-desulfation and 2-O-desulfation had no effect on heparin binding to K18, whereas 6-O-desulfation severely reduced binding, suggesting a critical role for 6-O-sulfation in the tau-heparin interaction. The tau-heparin interaction became stronger with longer-chain heparin oligosaccharides. As expected for an electrostatics-driven interaction, a moderate amount of salt (0.3 M NaCl) abolished binding. NMR showed the largest chemical-shift perturbation (CSP) in R2 in tau K18, which was absent in K19, revealing differential binding sites in K18 and K19 to heparin. Dermatan sulfate binding produced minimal CSP, whereas dermatan disulfate, with the additional 6-O-sulfo group, induced much larger CSP. 2-O-desulfated heparin induced much larger CSP in K18 than 6-O-desulfated heparin. Our data demonstrate a crucial role for the 6-O-sulfo group in the tau-heparin interaction, which to our knowledge has not been reported before.
dc.description.sponsorshipNational Institutes of Health
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofBiophysical Journal
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleGlycan Determinants of Heparin-Tau Interaction
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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