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Misfolded endoplasmic reticulum retained subunits cause degradation of wild‐type subunits of arylsulfatase A heteromers
Author(s) -
Poeppel Peter,
Abouzied Mekky Mohamed,
Völker Christof,
Gieselmann Volkmar
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07745.x
Subject(s) - endoplasmic reticulum , arylsulfatase a , protein subunit , sulfatase , arylsulfatase , biochemistry , wild type , microbiology and biotechnology , enzyme , biology , chemistry , mutant , gene
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.