Biological role of Smt3 conjugation

     We are interested in understanding the biological role of Smt3 conjugation. Smt3 is a small (~100 amino acid) protein with about 20% homology to ubiquitin. Like ubiquitin, it is attached to other proteins via an isopeptide linkage between its C-terminus and e-amino groups on the target proteins. While ubiquitylation of proteins targets them for proteasomal degradation, the purpose of Smt3 conjugation is not completely understood. Thus, far most studies appear to point to roles in targeting proteins to the proper cellular compartments. We have recently identified the Drosophila genes encoding the enzymatic machinery responsible for Smt3 conjugation (15). Using a combination of biochemical, molecular, and genetic analysis our goal is to illuminate the cellular and developmental roles of this process.

The pathways of ubiquitin and Smt3 conjugation. Ubiquitin and Smt3 conjugation occur by similar pathways. Both proteins are initially attached via a thioester linkage to an activating enzyme (E1 in the case of ubiquitin and SAE1/SAE2 in the case of Smt3). This activation reaction requires ATP hydrolysis. Smt3 and ubiquitin are then handed off to appropriate conjugating enzymes (E2 in the case of ubiquitin and Ubc9 in the case of Smt3), which transfer them to a protein substrate (indicated by the red circles containing the letter S). The role of ubiquitin conjugation is to target proteins for proteolysis, while the role