A family of novel, acidic N-glycans in Bowes melanoma tissue plasminogen activator have L2/HNK-1-bearing antennae, many with sulfation of the fucosylated chitobiose core.

Journal article

A family of about 20 novel acidic bi- and tri-antennary N-glycans, amounting to almost half those expressed on Bowes melanoma tissue-plasminogen activator (t-PA) were found to possess Galbeta1-->4GlcNAcbeta1-->, sulfated and sialylated GalNAcbeta1-->4GlcNAcbeta1--> or sulfated GlcAbeta1--> 3Galbeta1-->4GlcNAcbeta1--> antennae, of which those containing sulfated GlcA, depicting the L2/HNK-1 carbohydrate epitope, were preferentially located on the 6 arm. A proportion of the glycans were highly charged, because of multiple and variously distributed sulfation, some of which was located on the fucosylated chitobiose core. Multiple expression of the L2/HNK-1 epitope on a single glycan was observed. The most abundant compound was a biantennary glycan carrying sulfated GlcA on the 6-branched antenna and an alpha2-->6 sialylated GalNAc on the other. The N-glycosylation sequon containing Asn448, which is known to express all of the sulfate-carrying N-glycans contains, unusually, an arginine residue. An electrostatic interaction between this cationic amino acid and the core-sulfate group of the N-glycan is proposed to reduce mobility of the carbohydrate in the region of the t-PA active site. Because of the 'brain-type' nature of the N-glycans described in this neuro-ectodermal cell line, the possibility of neural t-PA interacting with the L2/HNK-1-recognizing molecule, laminin, of the central nervous system extracellular matrix is discussed.

Authors: Zamze, S; Wing, DR; Wormald, M; Hunter, A; Dwek, R

• Publication status: Published
• Journal: European journal of biochemistry / FEBS
• Volume: 268
• Issue: 14
• Pages: 4063-4078
• Publication date: 2001-07-01
• DOI: 10.1046/j.1432-1327.2001.02320.x
• EISSN: 1432-1033
• ISSN: 0014-2956
• Language: English
• Keywords: Epitopes; Molecular Sequence Data; Humans; Disaccharides; Tissue Plasminogen Activator; Melanoma; Fucose; Carbohydrate Sequence; Nerve Tissue; Antigens, CD57; Antigens, Tumor-Associated, Carbohydrate; Models, Molecular; Sulfuric Acid Esters