title: The amino-terminal sequences in the pro-alpha and -beta polypeptides of human lysosomal beta-hexosaminidase A and B are retained in the mature isozymes.
abstract: The alpha- and beta-subunits of beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52) are synthesized in the rough endoplasmic reticulum as prepropolypeptides. After the loss of the signal peptide and formation of enzymatically active dimers, the pro-isoenzymes are transported through the Golgi and into the lysosome for proteolytic and glycolytic processing to their stable mature forms. Maturation includes the hydrolysis, and previously presumed loss, of small N-terminal peptides from each propolypeptide. A recent report characterizing the processing of the beta-prepropolypeptide in beta-hexosaminidase from a human fibroblast cell line [(1989) J. Biol. Chem. 264, 3380-3384] reported that the small pro-beta peptide was retained through a disulfide bond in the mature subunit, and that it was glycosylated. We have confirmed this result in normal human tissue. However, we report a different N-terminal for the mature pro-beta peptide. Furthermore, we have found that the pro-alpha peptide is similarly retained in the mature alpha-subunit through its single cysteine residue and that each pro-peptide undergoes C-terminal processing.
authors.affiliation: Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Hubbes
authors.forename: J
authors.initials: J
authors.lastname: Callahan
authors.forename: R
authors.initials: R
authors.lastname: Gravel
authors.forename: D
authors.initials: D
authors.lastname: Mahuran
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D001619:beta-N-Acetylhexosaminidases / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007527:Isoenzymes; D010455:Peptides; D001619:beta-N-Acetylhexosaminidases