The molecular determinants for ubiquitin-specific recognition by USP2 and Ube1
Date Issued
2014
Date
2014
Author(s)
Jiang, Yi-Wei
Abstract
Ub and ubiquitin-like protein modification involve in lots of important physiological pathways. Of all known ubiquitin-like proteins, NEDD8 (Neuronal precursor cell Expressed, Developmentally Down-regulated 8) is the closest relative to ub in amino acid sequence identity. In spite of their highly identity, ub and NEDD8 participate in distinct pathways, indicating that they should be distinguished and activated by individual specific enzyme systems. Previous studies showed that ub-specific peptidase USP2 and NEDD8-specific peptidase SENP8 perform different substrate specificity for recognizing ub and NEDD8. By investigating the crystal structure of ub-USP2 binding complex and comparing the amino acid sequence of ub and NEDD8, residues 4, 12 and 14 of ub were proposed as important molecular determinants. Mutations at F4K, T12E and T14E of ub partially inhibited its hydrolysis by USP2. In this study, the experimental results further revealed that residues 4, 12, 14 and 72 of ub can also be the molecular determinants for specific recognition by ubiquitin E1 activating enzyme Ube1. The present data showed that Ube1 cannot catalyze the ubiquitin mutant with the simultaneous mutations at residues 4, 12, 14 and 72, suggesting that these four molecular determinants are conserved among different enzymes in the ubiquitin processing and activation pathways.
Subjects
泛素
NEDD8
USP2
Ube1
Type
thesis
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