title: Proteolytic processing of QSOX1A ensures efficient secretion of a potent disulfide catalyst.
abstract: QSOX1 (quiescin sulfhydryl oxidase 1) efficiently catalyses the insertion of disulfide bonds into a wide range of proteins. The enzyme is mechanistically well characterized, but its subcellular location and the identity of its protein substrates remain ill-defined. The function of QSOX1 is likely to involve disulfide formation in proteins entering the secretory pathway or outside the cell. In the present study, we show that this enzyme is efficiently secreted from mammalian cells despite the presence of a transmembrane domain. We identify internal cleavage sites and demonstrate that the protein is processed within the Golgi apparatus to yield soluble enzyme. As a consequence of this efficient processing, QSOX1 is probably functional outside the cell. Also, QSOX1 forms a dimer upon cleavage of the C-terminal domain. The processing of QSOX1 suggests a novel level of regulation of secretion of this potent disulfide catalyst and producer of hydrogen peroxide.
authors.affiliation: Institute of Molecular, Cellular and Systems Biology, College of Medical Veterinary and Life Sciences, University of Glasgow, UK.
authors.forename: Jana
authors.initials: J
authors.lastname: Rudolf
authors.forename: Marie A
authors.initials: MA
authors.lastname: Pringle
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Bulleid
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
chemical_list: D000939:Epitopes; D007527:Isoenzymes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C117183:QSOX1 protein, human