Conformational and dynamic changes at the interface contribute to ligand binding by ubiquitin.

Abstract

Ubiquitin interacts with numerous domains and motifs in its lifetime that vary in structure but bind the same hydrophobic patch. To identify the structural features of ubiquitin that make it an exceptional protein-protein interaction partner, we have studied the interaction of ubiquitin with the signal transducing adaptor molecule-1 ubiquitin interacting motif (UIM) using nuclear magnetic resonance. Our studies bring to light the role of the inherent backbone flexibility of ubiquitin in its interactions with a large array of binding partners, revealed from the changes in C(α) chemical shifts, backbone dynamics, and hydrogen bond lengths upon UIM binding. The crystal structures of ubiquitin complexes lend further support to our findings, underscoring the importance of the unique and flexible hydrogen bond network within ubiquitin and simultaneously providing insights into the nature of the slow motions. Taken together, our studies provide an in-depth view of the molecular changes associated with ligand recognition by ubiquitin.