Ubc9 sumoylation regulates SUMO target discrimination.
Posttranslational modification with small ubiquitin-related modifier, SUMO, is a widespread mechanism for rapid and reversible changes in protein function. Considering the large number of known targets, the number of enzymes involved in modification seems surprisingly low: a single E1, a single E2, and a few distinct E3 ligases. Here we show that autosumoylation of the mammalian E2-conjugating enzyme Ubc9 at Lys14 regulates target discrimination. While not altering its activity toward HDAC4, E2-25K, PML, or TDG, sumoylation of Ubc9 impairs its activity on RanGAP1 and strongly activates sumoylation of the transcriptional regulator Sp100. Enhancement depends on a SUMO-interacting motif (SIM) in Sp100 that creates an additional interface with the SUMO conjugated to the E2, a mechanism distinct from Ubc9 approximately SUMO thioester recruitment. The crystal structure of sumoylated Ubc9 demonstrates how the newly created binding interface can provide a gain in affinity otherwise provided by E3 ligases.
Pubmed ID: 18691969 RIS Download
Amino Acid Motifs | Amino Acid Sequence | Autoantigens | Crystallography, X-Ray | Esters | HeLa Cells | Humans | Models, Molecular | Molecular Sequence Data | Protein Structure, Secondary | Saccharomyces cerevisiae | Small Ubiquitin-Related Modifier Proteins | Substrate Specificity | Ubiquitin-Conjugating Enzymes