Substrate specificity of the oxidoreductase ERp57 is determined primarily by its interaction with calnexin and calreticulin
| Autor: | Joseph E. Chambers, Catherine E. Jessop, Rachel H. Watkins, Neil J. Bulleid, Timothy J. Tavender |
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| Rok vydání: | 2008 |
| Předmět: |
Protein Folding
Protein Disulfide-Isomerase Family Calnexin Protein Disulfide-Isomerases Biochemistry Cell Line Substrate Specificity 03 medical and health sciences Mice Oxidoreductase Animals Humans Disulfides Protein disulfide-isomerase Molecular Biology Secretory pathway 030304 developmental biology chemistry.chemical_classification Mice Knockout 0303 health sciences biology Endoplasmic reticulum Integrin beta1 Protein Synthesis Post-Translational Modification and Degradation 030302 biochemistry & molecular biology Cell Biology Cell biology chemistry Mutation biology.protein Glycoprotein Calreticulin Oxidation-Reduction Protein Binding |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Popis: | The formation of disulfides within proteins entering the secretory pathway is catalyzed by the protein disulfide isomerase family of endoplasmic reticulum localized oxidoreductases. One such enzyme, ERp57, is thought to catalyze the isomerization of non-native disulfide bonds formed in glycoproteins with unstructured disulfide-rich domains. Here we investigated the mechanism underlying ERp57 specificity toward glycoprotein substrates and the interdependence of ERp57 and the calnexin cycle for their correct folding. Our results clearly show that ERp57 must be physically associated with the calnexin cycle to catalyze isomerization reactions with most of its substrates. In addition, some glycoproteins only require ERp57 for correct disulfide formation if they enter the calnexin cycle. Hence, the specificity of ER oxidoreductases is not only determined by the physical association of enzyme and substrate but also by accessory factors, such as calnexin and calreticulin in the case of ERp57. These conclusions suggest that the calnexin cycle has evolved with a specialized oxidoreductase to facilitate native disulfide formation in complex glycoproteins. |
| Databáze: | OpenAIRE |
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