Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides
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Authors
Miller, Michelle C.
Cai, Chao
Wichapong, Kanin
Bhaduri, Sayantan
Pohl, Nicola L.B.
Linhardt, Robert J.
Gabius, Hans Joachim
Mayo, Kevin H.
Issue Date
2020-12-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Glycosaminoglycan 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.
Description
Science Reports, 10, 15708
Note : 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.
Note : 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.
Full Citation
Structural 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.
Publisher
Nature
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
20452322