The three-dimensional glycan structures dynamically fluctuate in aqueous solutions. The dynamics of these molecular structures govern the interactions with sugar-recognizing molecules and are deeply involved in regulating the functions of sugar-bearing proteins. In glycotechnology and drug discovery targeting the glycan recognition systems, it is crucial to quantitatively understand the conformation of glycans bound to target molecules and the three-dimensional structural dynamics of unbound glycans. By modifying the conformational space of unbound glycans, it is possible to improve their affinity for lectins. Furthermore, the glycans constituting a glycoprotein also influence the conformational dynamics of the protein part. Therefore, in the molecular design of glycoproteins aiming for higher functionality, it is essential to consider the existence of an intramolecular interaction network where the glycan chains and the protein are integrated. Approaches from the perspective of experimental science, computational science, and information science will become increasingly important to decipher the biological information carried by the four-dimensional structures of glycans.

Integrins are αβ dimeric extracellular matrix receptors that exhibit a broad ligand specificity and function in various biological processes, including embryonic morphogenesis, cell migration, inflammatory responses, the malignant transformation of cancer, and invasive metastasis. Integrins are also crucial as carriers of N-glycans. In this mini review, we discuss the functions of N-glycans with a particular focus on integrins. The importance of glycans for integrins has been demonstrated using inhibitor experiments and the overexpression, knockdown, and knockout of glycosyltransferases. Furthermore, specific stimuli in a cancer stimulation have been shown to induce the expression of glycosyltransferases. As a result, the remodeled N-glycosylation of integrins regulate biological functions. To distinguish the significance of individual glycans from all glycan epitopes, our research group prepared an underglycosylated mutant and reintroduced it into integrin-deficient cells. The N-glycosylation of integrins is involved not only in cell adhesion, but also in cell-specific functions, such as cell migration, cell proliferation signaling, endocytosis, tumorigenesis, and malignant transformation. Bisecting- and β1,6-N-acetylglucosamine branching and terminal sialylation modifications in integrins are essential for these functions. Therefore, the N-glycosylation of integrins appears to be involved in diverse cellular functions.

The three-dimensional glycan structures dynamically fluctuate in aqueous solutions. The dynamics of these molecular structures govern the interactions with sugar-recognizing molecules and are deeply involved in regulating the functions of sugar-bearing proteins. In glycotechnology and drug discovery targeting the glycan recognition systems, it is crucial to quantitatively understand the conformation of glycans bound to target molecules and the three-dimensional structural dynamics of unbound glycans. By modifying the conformational space of unbound glycans, it is possible to improve their affinity for lectins. Furthermore, the glycans constituting a glycoprotein also influence the conformational dynamics of the protein part. Therefore, in the molecular design of glycoproteins aiming for higher functionality, it is essential to consider the existence of an intramolecular interaction network where the glycan chains and the protein are integrated. Approaches from the perspective of experimental science, computational science, and information science will become increasingly important to decipher the biological information carried by the four-dimensional structures of glycans.

Integrins are αβ dimeric extracellular matrix receptors that exhibit a broad ligand specificity and function in various biological processes, including embryonic morphogenesis, cell migration, inflammatory responses, the malignant transformation of cancer, and invasive metastasis. Integrins are also crucial as carriers of N-glycans. In this mini review, we discuss the functions of N-glycans with a particular focus on integrins. The importance of glycans for integrins has been demonstrated using inhibitor experiments and the overexpression, knockdown, and knockout of glycosyltransferases. Furthermore, specific stimuli in a cancer stimulation have been shown to induce the expression of glycosyltransferases. As a result, the remodeled N-glycosylation of integrins regulate biological functions. To distinguish the significance of individual glycans from all glycan epitopes, our research group prepared an underglycosylated mutant and reintroduced it into integrin-deficient cells. The N-glycosylation of integrins is involved not only in cell adhesion, but also in cell-specific functions, such as cell migration, cell proliferation signaling, endocytosis, tumorigenesis, and malignant transformation. Bisecting- and β1,6-N-acetylglucosamine branching and terminal sialylation modifications in integrins are essential for these functions. Therefore, the N-glycosylation of integrins appears to be involved in diverse cellular functions.