Ubc9 sumoylation regulates SUMO target discrimination
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Molecular Cell |
Volume | 31 |
Issue number | 3 |
Pages (from-to) | 371-82 |
Number of pages | 11 |
ISSN | 1097-2765 |
DOIs | |
Publication status | Published - 2008 |
Externally published | Yes |
Bibliographical note
Keywords: 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
ID: 16275371