RESUMO
Arylsulfatase A is an oligomeric lysosomal enzyme. In the present study, we use this enzyme as a model protein to examine how heteromerization of wild-type and misfolded endoplasmic reticulum-degraded arylsulfatase A polypeptides affects the quality control of wild-type arylsulfatase A subunits. Using a conformation sensitive monoclonal antibody, we show that, within heteromers of misfolded and wild-type arylsulfatase A, the wild-type subunits are not fully folded. The results obtained show that arylsulfatase A polypeptide complexes, rather than the monomers, are subject to endoplasmic reticulum quality control and that, within a heteromer, the misfolded subunit exerts a dominant negative effect on the wild-type subunit. Although it has been shown that mature lysosomal arylsulfatase A forms dimers at neutral pH, the results obtained in the present study demonstrate that, in the early biosynthetic pathway, arylsulfatase A forms oligomers with more than two subunits.
