The baculovirus Autographa californica nuclear polyhedrosis virus potentially encodes approximately 100 proteins. One of these proteins has high homology to the eukaryotic protein ubiquitin. Ubiquitin is an abundant protein that participates in or regulates a number of important cell processes. Ubiquitin is highly conserved and varies by only three amino acids between mammals, yeast and plants. It is believed that this conservation of sequence is mandated by the multiple function of ubiquitin. The viral protein, however, differs from mammalian ubiquitin at 18 amino acid residues, although many of the residues known to be essential for ubiquitin function have been conserved. The genomic structure of viral ubiquitin is also unique in that the viral gene encodes a monoubiquitin protein whereas all other ubiquitin genes described so far encode polyproteins or fusion proteins. These observations raise interesting questions with respect to why the viral protein has diverged from eukaryotic ubiquitin and why the virus encodes its own ubiquitin gene when ubiquitin is already present in the host cell. The basic goal of this project is to answer the following question: What is the function of viral ubiquitin and how is that function related to the amino acid sequence? One possibility is that the viral protein has a unique function, for example it could inhibit the host ubiquitin ligation system, disrupting many normal cell functions. Alternatively the viral protein may function in some, but not all, of the roles normally associated with ubiquitin, thereby relieving the evolutionary pressure to maintain the canonical sequence. We intend to address these questions through the use of monoclonal antibodies specific for the host and viral ubiquitins; construction of ubiquitin-deficient viral mutants; and in vitro assays of ubiquitin function using purified viral and host proteins.
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