Definitive evidence that a single N-glycan among three glycans on inducible costimulator is required for proper protein trafficking and ligand binding |
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Authors: | Naoki Kamei Yoshiyuki Suzuki Mitsuhiro Kinoshita Hironobu Hojo Takashi Tsuji |
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Institution: | a Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan b Department of Chemistry, Graduate School of Sciences, Osaka University, Machikaneyama, Toyonaka 560-0043, Japan c Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Osaka 577-8502, Japan d Department of Applied Biochemistry, Institute of Glycoscience, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan e Research Project for Glycoprotein Engineering Funded by Otsuka Chemical Co., Ltd., Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan f Glycotechnology Laboratory, Otsuka Chemical Co., Ltd., 134, Chudoji minami-machi, Shimogyo-ku, Kyoto 600-8815, Japan g Organ Technologies Inc., Tokyo 101-0048, Japan |
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Abstract: | Glycosylation is a widespread post-translational modification found in glycoproteins. Glycans play key roles in protein folding, quality control in the endoplasmic reticulum (ER) and protein trafficking within cells. However, it remains unclear whether all positions of protein glycosylation are involved in glycan functions, or if specific positions have individual roles. Here we demonstrate the integral involvement of a specific N-glycan from amongst the three glycans present on inducible costimulator (ICOS), a T-cell costimulatory molecule, in proper protein folding and intracellular trafficking to the cell surface membrane. We found that glycosylation-defective mutant proteins lacking N-glycan at amino-acid position 89 (N89), but not proteins lacking either N23 or N110, were retained within the cell and were not detected on the cell surface membrane. Additional evidence suggested that N89 glycosylation was indirectly involved in ICOS ligand binding. These data suggest that amongst the three putative ICOS glycosylation sites, N89 is required for proper ICOS protein folding in the ER, intracellular trafficking and ligand binding activity. This study represents a substantial contribution to the current mechanistic understanding of the necessity and potential functions of a specific N-glycan among the multiple glycans of glycoproteins. |
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Keywords: | N-Glycosylation Costimulatory molecule Inducible costimulator (ICOS) Protein trafficking Protein quality control |
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