Research Team Uncovers Molecular Code for Glycosylation

Many proteins in nature exist as glycoproteins, which consist of protein, or polypeptide chain, and glycan, the sugar chain. The protein structure is determined by its genetic blueprint, but the information on glycans is not directly encoded by the genome. Therefore, it is difficult to control protein glycosylation. 

However, researchers recently identified a molecular code embedded in protein for regulating its glycosylation.  The group, which includes researchers at Nagoya City University, National Institutes of Natural Sciences, and Academia Sinica, has found a specific amino acid sequence in a polypeptide that induces a specific glycan structure called Lewis X.

The researchers in Japan previously found that Lewis X specifically modifies the protein LAMP-1 in mouse neural stem cells through the enzymatic action of fucosyltransferase 9 (FUT9). In this recent study, they have shown that Lewis X modification specific for LAMP-1 occurs not only in neural stem cells but also in several cultured mammalian cells. Furthermore, they have found that a sequence consisting of 29-amino-acid residues in LAMP-1 promotes Lewis X modification catalyzed by the enzyme, and this sequence induces Lewis X modification when fused to other proteins used as biopharmaceuticals.

This means that, in glycoprotein molecules, a specific amino-acid sequence can determine their glycan structures.

Most of biopharmaceuticals are glycoproteins, as best exemplified by therapeutic antibodies, and their glycan structures are critical for efficacy and safety. Therefore, the findings, published recently in Communications Biology, pave the way for controlling glycosylation of biopharmaceuticals.