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https://hdl.handle.net/2115/87273

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

英語

2022-10-23

Nature Portfolio

Scientific reports

12(1)

17800

Dystroglycan (DG), which constitutes a part of the dystrophin-glycoprotein complex, connects the extracellular matrix to the cytoskeleton. The matriglycans presented by the extracellular alpha-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 (GlcNAc beta 1-2Man) 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 alpha-DG fragment (372)TRGAIIQTPTLGPIQPTRV(390) 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 alpha-DG core M1 glycoconjugates by cis-binding (via peptide- and carbohydrate-protein interactions), which can be abrogated by alpha 2,3-sialylation of the LacNAc units. The LacNAc-terminated alpha-DG glycopeptide interact simultaneously with both the S- and F-faces of Gal-1, thereby inducing oligomerization. Furthermore, Gal-1 can trans-bridge alpha-DG core M1 structures and laminins, which proposed a possible mechanism by which Gal-1 ameliorates muscular dystrophies; however, this proposal warrants further investigation.

学術雑誌論文

Version of Record

2045-2322