Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides
| Autor: | Nicola L. B. Pohl, Sayantan Bhaduri, Robert J. Linhardt, Kevin H. Mayo, Chao Cai, Hans-Joachim Gabius, Michelle C. Miller, Kanin Wichapong |
|---|---|
| Přispěvatelé: | Biochemie, RS: Carim - B01 Blood proteins & engineering |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Keratan sulfate Galectins Disaccharide Biophysics lcsh:Medicine Plasma protein binding Molecular Dynamics Simulation Biochemistry Article Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound Molecular recognition DIVERSE ROLES CHONDROITIN SULFATE Humans GLYCAN RECOGNITION CELL Binding site lcsh:Science Nuclear Magnetic Resonance Biomolecular Galectin POLY-N-ACETYLLACTOSAMINE Glycosaminoglycans Multidisciplinary Binding Sites 030102 biochemistry & molecular biology biology GLYCOSYLATION lcsh:R Lectin LECTIN 030104 developmental biology chemistry P53-INDUCED GENE-1 Keratan Sulfate biology.protein lcsh:Q LIGANDS Proteoglycans Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, 10(1):15708. Nature Publishing Group Scientific Reports, Vol 10, Iss 1, Pp 1-18 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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