earticle

영어

Glycosylation is a major post-translational protein modification, which alters physicochemical properties of the protein, affecting the folding, distribution, stability and thus biological function and efficiency of protein. Nglycosylation begins in the endoplasmic reticulum (ER) with the synthesis and the co-translational transfer of a lipidlinked oligosaccharide precursor to specific asparagine (N) residues of the nascent polypeptide chain. During the maturation in the ER and the Golgi complex, N-glycans can be further modified by glycosidases and glycosyltransferases until the glycoprotein arrives in its final destination. After their maturation, some plant type
complex N-glycans are distinctive from those found in mammalian because they contain β1,2-xylose and core α1,3-fucose residues attached to the pentasaccharide (Man3GlcNAc2) core structure but no sialic acid residues. The presence of β1,2-xylose and core α1,3-fucose residues on plant type complex N-glycans has long been an irritating limitation in the use of plant-made pharmaceuticals (PMPs) in human therapy, as these N-glycan epitopes are
potentially immunogenic in mammals. However, considerable improvement has been made towards humanization of N-glycosylation in plants to remove the potential limits of plant cells as a factory for the production of pharmaceutical glycoproteins. The addition of the potentially immunogenic β1,2-xylose and core α1,3-fucose residues on plant-made pharmaceuticals may be avoided when the expressions of responsible glycosyltransferases have been interfered or
removed by RNA interference (RNAi) or gene knockout techniques, respectively. Alternatively, cgl mutants lacking N-acetylglucosaminyltransferase I (GnTI) activity synthesize only oligomannosidic N-glycans and ER retention of the recombinant protein may be used to restrict glycosylation of target proteins to only high-mannose type N-glycans. In addition, N-glycosylation also plays important roles in the quality control (QC) of glycoprotein folding in the ER lumen and in ER-associated degradation (ERAD) of proteins by cytosolic proteasomes. Protein QC in the ER lumen is functionally linked to unfolded protein response (UPR), namely, an increase of misfolded protein in the ER is sensed as an ‘ER stress’ and induces increased synthesis of UPR- and ERAD-associated genes. Plants are emerging as a substitute system for the pharmaceutical protein production because of their practical, economic and safety advantages. However, the limitations of plants as a pharmaceutical protein production system should be carefully considered and ameliorated. (Supported by BK21 program)