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The amino‐terminal sequences in the pro‐α and ‐β polypeptides of human lysosomal β‐hexosaminidase A and B are retained in the mature isozymes
Author(s) -
Hubbes Martin,
Callahan John,
Gravel Roy,
Mahuran Don
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80649-0
Subject(s) - peptide , biochemistry , protein subunit , endoplasmic reticulum , signal peptide , cysteine , golgi apparatus , isozyme , chemistry , lysosome , hexosaminidase , peptide sequence , biology , enzyme , gene
The α‐ and β‐subunits of β‐hexosaminidase (β‐ 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 β‐prepropolypeptide in β‐hexosaminidase from a human fibroblast cell line [(1989) J. Biol. Chem. 264, 3380–3384] reported that the small pro‐β 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‐β peptide. Furthermore, we have found that the pro‐α peptide is similarly retained in the mature α‐subunit through its single cysteine residue and that each pro‐peptide undergoes C‐terminal processing.