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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorMiller, Michelle C.
dc.contributor.authorCai, Chao
dc.contributor.authorWichapong, Kanin
dc.contributor.authorBhaduri, Sayantan
dc.contributor.authorPohl, Nicola L.B.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorGabius, Hans Joachim
dc.contributor.authorMayo, Kevin H.
dc.identifier.citationStructural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides, M. C. Miller, C. Cai, K. Wichapong, S. Bhaduri, N. L.B. Pohl, R. J. Linhardt, H. -J. Gabius, K. H. Mayo, Science Reports, 10, 15708, 2020.
dc.descriptionScience Reports, 10, 15708
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.abstractGlycosaminoglycan chains of keratan sulfate proteoglycans appear to be physiologically significant by pairing with tissue lectins. Here, we used NMR spectroscopy and molecular dynamics (MD) simulations to characterize interactions of corneal keratan sulfate (KS), its desulfated form, as well as di-, tetra- (N-acetyllactosamine and lacto-N-tetraose) and octasaccharides with adhesion/growth-regulatory galectins, in particular galectin-3 (Gal-3). The KS contact region involves the lectin canonical binding site, with estimated KD values in the low µM range and stoichiometry of ~ 8 to ~ 20 galectin molecules binding per polysaccharide chain. Compared to Gal-3, the affinity to Gal-7 is relatively low, signaling preferences among galectins. The importance of the sulfate groups was delineated by using desulfated analogs that exhibit relatively reduced affinity. Binding studies with two related di- and tetrasaccharides revealed a similar decrease that underscores affinity enhancement by repetitive arrangement of disaccharide units. MD-based binding energies of KS oligosaccharide-loaded galectins support experimental data on Gal-3 and -7, and extend the scope of KS binding to Gal-1 and -9N. Overall, our results provide strong incentive to further probe the relevance of molecular recognition of KS by galectins in terms of physiological processes in situ, e.g. maintaining integrity of mucosal barriers, intermolecular (lattice-like) gluing within the extracellular meshwork or synaptogenesis.
dc.description.sponsorshipNational Science Foundation
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofScientific Reports
dc.rightsAttribution 3.0 United States*
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleStructural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharidesen_US
dcterms.accessRightsOpen Access
dcterms.accessRightsA full text version is available in DSpace@RPI
dc.rights.holderCC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
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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