Identification of amino acid residues in a class I ubiquitin-conjugating enzyme involved in determining specificity of conjugation of ubiquitin to proteins.

The Journal of Biological Chemistry
Rose OughtredS S Wing

Abstract

The ubiquitin pathway is a major system for selective proteolysis in eukaryotes. However, the mechanisms underlying substrate selectivity by the ubiquitin system remain unclear. We previously identified isoforms of a rat ubiquitin-conjugating enzyme (E2) homologous to the Saccharomyces cerevisiae class I E2 genes, UBC4/UBC5. Two isoforms, although 93% identical, show distinct features. UBC4-1 is expressed ubiquitously, whereas UBC4-testis is expressed in spermatids. Interestingly, although these isoforms interacted similarly with some ubiquitin-protein ligases (E3s) such as E6-AP and rat p100 and an E3 that conjugates ubiquitin to histone H2A, they also supported conjugation of ubiquitin to distinct subsets of testis proteins. UBC4-1 showed an 11-fold greater ability to support conjugation of ubiquitin to endogenous substrates present in a testis nuclear fraction. Site-directed mutagenesis of the UBC4-testis isoform was undertaken to identify regions of the molecule responsible for the observed difference in substrate specificity. Four residues (Gln-15, Ala-49, Ser-107, and Gln-125) scattered on surfaces away from the active site appeared necessary and sufficient for UBC4-1-like conjugation. These four residues identify a large...Continue Reading

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Citations

Mar 16, 2005·Molecular and Cellular Biology·Zhiqian LiuSimon S Wing
Aug 14, 2001·Biochemical and Biophysical Research Communications·S N BoccaP Wappner
Jun 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·L VerPlankC A Carter
Sep 7, 2002·The Journal of Biological Chemistry·Martin ObinAllen Taylor

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