The interaction between small ubiquitin-related modifier SUMO and its conjugating-enzyme Ubc9 (E2) is an essential step in SUMO conjugation cascade. However, an experimental structure of such a transient complex is still unavailable. Here, a structural model of SUMO-3-Ubc9 complex was obtained with HADDOCK, combining NMR chemical shift mapping information. Docking calculations were performed using SUMO-3 and Ubc9 structures as input. The resulting complex reveals that the complementary surface electrostatic potentials contribute dominantly to the specific interaction. At the interface, similar numbers of oppositely-charged conserved residues are identified on the respective binding partners. Hydrogen bonds are formed in the vicinity of the interface to stabilize the complex. Comparison of the structure of SUMO-3-Ubc9 complex generated by HADDOCK and the experimental structures in free form indicates that SUMO-3 and Ubc9 maintain their respective fold as a whole after docking. However, the N-terminal helix alpha1 and its subsequent L1 loop of Ubc9 experience sizeable changes upon complex formation. They cooperatively move towards the hydrophilic side of the beta-sheet of SUMO-3. Our observations are consistent with the data from previous Ubc9 mutational analysis and conformational flexibility studies. Together, we have proposed that the SUMO-3-Ubc9 interaction is strongly electrostatically driven and the N terminus of Ubc9 shifts to SUMO-3 to facilitate the interaction. The NMR-based structural model, which provides considerable insights into the molecular basis of the specific SUMO-E2 recognition and interaction, implicates the general interaction mode between SUMO-3 and Ubc9 homologues from yeast to humans.

• PMID: 16224784
• DOI full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Ding H, Yang Y, Zhang J, Wu J, Liu H, Shi Y

Primary Lit For

Additional Lit For

Review For