| Abstract
| - Ubiquitination plays important roles in a variety of biological processes, such as DNA repair,cell cycle regulation, and p53-dependent processes. Despite intensive studies in ubiquitination, themechanism of substrate recognition is still not well understood. Each E2 has its own substrate specificity,yet substrate proteins recognized by each E2 are highly diverse. To better understand how E2 proteinsconfer both substrate specificity and diversity, we have studied conformational flexibility of an E2, UBC9,using nuclear magnetic resonance 15N relaxation and hydrogen−deuterium exchange measurements. Tworegions in human UBC9 show higher mobility over a wide range of time scales. Combined with previousbiochemical studies, both regions are likely to be important for protein−protein recognition in the ubiquitinpathway. The region near the N-terminus may be important for interactions with the E1-UBL1 conjugate.The region near the C-terminus, which undergoes conformational exchange may be important for substratebinding and catalytic activity. Since E2 enzymes share high homology in primary sequences and three-dimensional structures, the conformational flexibility of UBC9 may represent a general feature of E2enzymes. This study provides a new perspective for further studies of protein−protein recognition inubiquitination.
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