Molecular Heterogeneity in O-Variant GM2 Gangliosidosis
The hydrolysis of GM2-ganglioside by β-hexosaminidase A (Hex A) is unique in its requirement for the proper synthesis and posttranslational processing of three different gene products. Two of these code for the pre-α and β polypeptides that combine to produce active pre-Hex A. The third is a specific Hex A activator protein required to complex with the natural substrate, GM2-ganglioside. Synthesis of mature Hex A and Hex B, the other major Hex isozyme in normal cells composed of only β-subunits, requires processing through the ER and Golgi apparatus with final sequestering in the lysosome. As a result of proteolytic processing in the lysosome the structures of the mature forms of Hex A and Hex B are α(βaβb) and 2(βaβb), where the pre-β chain is proteolytically split into covalently bound nonidentical βa and βb segments.
KeywordsDeletion Line Mutant Cell Line Sandhoff Disease Juvenile Patient Infantile Type
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