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Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan. | LitMetric

Exploring the In situ pairing of human galectins toward synthetic O-mannosylated core M1 glycopeptides of α-dystroglycan.

Sci Rep

Frontier Research Center for Advanced Material and Life Science, Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University, N21, W11, Sapporo, 001-0021, Japan.

Published: October 2022

AI Article Synopsis

Article 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 TRGAIIQTPTLGPIQPTRV 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588787PMC
http://dx.doi.org/10.1038/s41598-022-22758-0DOI Listing

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