Abstract
Ubiquitin C-terminal hydrolase Ll is a a deubiquitinating enzyme (DUB) found primarily in the CNS, making up about 2% of soluble brain tissue. Mutations in UCH-Ll have been associated with both neurodegenerative and neuroprotective phenotypes, and upregulation of activity has been linked to malignancies. Recent evidence suggests that a UCH-Ll dimer may exhibit altered hydrolase activity relative to the monomer, as well as possible ligase activity. Here, we investigated the structure and activity of a synthetic UCH-Ll dimer. In addition to dimers, we found evidence of tetramers and higher order oligomers. Hydrolase activity of the dimer was found to be six times lower than that of the monomer.