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Structural basis for SUMO-E2 interaction revealed by a complex model using docking approach in combination with NMR data.

Husheng Ding·Yuedong Yang·Jiahai Zhang·Jihui Wu·Haiyan Liu·Yunyu Shi
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Abstract

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.

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Binding SitesCalorimetryKineticsModels, MolecularProtein Structure, SecondarySmall Ubiquitin-Related Modifier ProteinsStatic ElectricityThermodynamicsUbiquitin-Conjugating EnzymesUbiquitin-Conjugating Enzyme UBC9Journal ArticleResearch Support, Non-U.S. Gov't

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Husheng Ding, Yuedong Yang, Jiahai Zhang, Jihui Wu, Haiyan Liu, Yunyu Shi. 2005-12-01. Structural basis for SUMO-E2 interaction revealed by a complex model using docking approach in combination with NMR data.. https://doi.org/10.1002/prot.20695

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