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Structural basis for SUMO‐E2 interaction revealed by a complex model using docking approach in combination with NMR data
Author(s) -
Ding Husheng,
Yang Yuedong,
Zhang Jiahai,
Wu Jihui,
Liu Haiyan,
Shi Yunyu
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20695
Subject(s) - docking (animal) , chemistry , stereochemistry , protein–protein interaction , hydrogen bond , active site , enzyme , molecule , biochemistry , medicine , nursing , organic chemistry
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 α1 and its subsequent L1 loop of Ubc9 experience sizeable changes upon complex formation. They cooperatively move towards the hydrophilic side of the β‐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. Proteins 2005. © 2005 Wiley‐Liss, Inc.