Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming

HECT E3 ligases directly catalyze ubiquitin transfer to their substrates. The crystal structure of ubiquitin-loaded Nedd4 HECT domain in complex with ubiquitin is now presented, revealing insights into the mechanisms for catalytic priming and sequential addition and suggesting the basis for Lys63 specificity.