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Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanism by which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3:E2∼Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2∼Ub ensembles toward closed conformations with...
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