Cargando…
Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides
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-,...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515912/ https://www.ncbi.nlm.nih.gov/pubmed/32973213 http://dx.doi.org/10.1038/s41598-020-72645-9 |
_version_ | 1783586901076213760 |
---|---|
author | Miller, Michelle C. Cai, Chao Wichapong, Kanin Bhaduri, Sayantan Pohl, Nicola L. B. Linhardt, Robert J. Gabius, Hans-Joachim Mayo, Kevin H. |
author_facet | Miller, Michelle C. Cai, Chao Wichapong, Kanin Bhaduri, Sayantan Pohl, Nicola L. B. Linhardt, Robert J. Gabius, Hans-Joachim Mayo, Kevin H. |
author_sort | Miller, Michelle C. |
collection | PubMed |
description | 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 K(D) 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. |
format | Online Article Text |
id | pubmed-7515912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75159122020-09-29 Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides Miller, Michelle C. Cai, Chao Wichapong, Kanin Bhaduri, Sayantan Pohl, Nicola L. B. Linhardt, Robert J. Gabius, Hans-Joachim Mayo, Kevin H. Sci Rep Article 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 K(D) 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. Nature Publishing Group UK 2020-09-24 /pmc/articles/PMC7515912/ /pubmed/32973213 http://dx.doi.org/10.1038/s41598-020-72645-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Miller, Michelle C. Cai, Chao Wichapong, Kanin Bhaduri, Sayantan Pohl, Nicola L. B. Linhardt, Robert J. Gabius, Hans-Joachim Mayo, Kevin H. Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
title | Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
title_full | Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
title_fullStr | Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
title_full_unstemmed | Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
title_short | Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
title_sort | structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515912/ https://www.ncbi.nlm.nih.gov/pubmed/32973213 http://dx.doi.org/10.1038/s41598-020-72645-9 |
work_keys_str_mv | AT millermichellec structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT caichao structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT wichapongkanin structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT bhadurisayantan structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT pohlnicolalb structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT linhardtrobertj structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT gabiushansjoachim structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides AT mayokevinh structuralinsightintothebindingofhumangalectinstocornealkeratansulfateitsdesulfatedformandrelatedsaccharides |