Employing 125 I-polyubiquitin chain formation as a functional readout of ligase activity,
biochemical and biophysical evidence demonstrates that catalytically active E6-associated
protein (E6AP)/UBE3A is an oligomer. Based on an extant structure previously discounted
as an artifact of crystal packing forces, we propose that the fully active form of E6AP is a
trimer, analysis of which reveals a buried surface of 7508 Å 2 and radially symmetric
interacting residues that are conserved within the Hect (homologous to E6AP C terminus) …