Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan
Abstract Dystroglycan (DG), which constitutes a part of the dystrophin–glycoprotein complex, connects the extracellular matrix to the cytoskeleton. The matriglycans presented by the extracellular α-DG serve as a contact point with extracellular matrix proteins (ECM) containing laminin G-like domains...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22758-0 |
| _version_ | 1811336561786093568 |
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| author | Lareno L. Villones Anna-Kristin Ludwig Hiroyuki Kumeta Seiya Kikuchi Rika Ochi Tomoyasu Aizawa Shin-Ichiro Nishimura Hans-Joachim Gabius Hiroshi Hinou |
| author_facet | Lareno L. Villones Anna-Kristin Ludwig Hiroyuki Kumeta Seiya Kikuchi Rika Ochi Tomoyasu Aizawa Shin-Ichiro Nishimura Hans-Joachim Gabius Hiroshi Hinou |
| author_sort | Lareno L. Villones |
| collection | DOAJ |
| description | Abstract Dystroglycan (DG), which constitutes a part of the dystrophin–glycoprotein complex, connects the extracellular matrix to the cytoskeleton. The matriglycans presented by the extracellular α-DG serve as a contact point with extracellular matrix proteins (ECM) containing laminin G-like domains, providing cellular stability. However, it remains unknown whether core M1 (GlcNAcβ1-2Man) structures can serve as ligands among the various O-Mannosylated glycans. Therefore, based on the presence of N-acetylLactosamine (LacNAc) in this glycan following the core extension, the binding interactions with adhesion/growth-regulatory galectins were explored. To elucidate this process, the interaction between galectin (Gal)-1, -3, -4 and -9 with α-DG fragment 372TRGAIIQTPTLGPIQPTRV390 core M1-based glycopeptide library were profiled, using glycan microarray and nuclear magnetic resonance studies. The binding of galectins was revealed irrespective of its modular architecture, adding galectins to the list of possible binding partners of α-DG core M1 glycoconjugates by cis-binding (via peptide- and carbohydrate-protein interactions), which can be abrogated by α2,3-sialylation of the LacNAc units. The LacNAc-terminated α-DG glycopeptide interact simultaneously with both the S- and F-faces of Gal-1, thereby inducing oligomerization. Furthermore, Gal-1 can trans-bridge α-DG core M1 structures and laminins, which proposed a possible mechanism by which Gal-1 ameliorates muscular dystrophies; however, this proposal warrants further investigation. |
| first_indexed | 2024-04-13T17:41:17Z |
| format | Article |
| id | doaj.art-3b313ae12f4c4ebbae078d91bb584ce4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T17:41:17Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3b313ae12f4c4ebbae078d91bb584ce42022-12-22T02:37:10ZengNature PortfolioScientific Reports2045-23222022-10-0112111610.1038/s41598-022-22758-0Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycanLareno L. Villones0Anna-Kristin Ludwig1Hiroyuki Kumeta2Seiya Kikuchi3Rika Ochi4Tomoyasu Aizawa5Shin-Ichiro Nishimura6Hans-Joachim Gabius7Hiroshi Hinou8Frontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityPhysiological Chemistry, Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-University MunichFrontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityFrontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityFrontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityFrontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityFrontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityPhysiological Chemistry, Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-University MunichFrontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido UniversityAbstract Dystroglycan (DG), which constitutes a part of the dystrophin–glycoprotein complex, connects the extracellular matrix to the cytoskeleton. The matriglycans presented by the extracellular α-DG serve as a contact point with extracellular matrix proteins (ECM) containing laminin G-like domains, providing cellular stability. However, it remains unknown whether core M1 (GlcNAcβ1-2Man) structures can serve as ligands among the various O-Mannosylated glycans. Therefore, based on the presence of N-acetylLactosamine (LacNAc) in this glycan following the core extension, the binding interactions with adhesion/growth-regulatory galectins were explored. To elucidate this process, the interaction between galectin (Gal)-1, -3, -4 and -9 with α-DG fragment 372TRGAIIQTPTLGPIQPTRV390 core M1-based glycopeptide library were profiled, using glycan microarray and nuclear magnetic resonance studies. The binding of galectins was revealed irrespective of its modular architecture, adding galectins to the list of possible binding partners of α-DG core M1 glycoconjugates by cis-binding (via peptide- and carbohydrate-protein interactions), which can be abrogated by α2,3-sialylation of the LacNAc units. The LacNAc-terminated α-DG glycopeptide interact simultaneously with both the S- and F-faces of Gal-1, thereby inducing oligomerization. Furthermore, Gal-1 can trans-bridge α-DG core M1 structures and laminins, which proposed a possible mechanism by which Gal-1 ameliorates muscular dystrophies; however, this proposal warrants further investigation.https://doi.org/10.1038/s41598-022-22758-0 |
| spellingShingle | Lareno L. Villones Anna-Kristin Ludwig Hiroyuki Kumeta Seiya Kikuchi Rika Ochi Tomoyasu Aizawa Shin-Ichiro Nishimura Hans-Joachim Gabius Hiroshi Hinou Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan Scientific Reports |
| title | Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan |
| title_full | Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan |
| title_fullStr | Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan |
| title_full_unstemmed | Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan |
| title_short | Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan |
| title_sort | exploring the in situ pairing of human galectins toward synthetic o mannosylated core m1 glycopeptides of α dystroglycan |
| url | https://doi.org/10.1038/s41598-022-22758-0 |
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