{"doi":"10.1073/pnas.1415621112","title":"Distinct activation of an E2 ubiquitin-conjugating enzyme by its cognate E3 ligases","abstract":"Significance\n Ubiquitin (Ub) conjugation triggers protein degradation by the proteasome. Here we describe an unexplored feature of the Ub conjugation system that entails differential activation of an E2-conjugating enzyme by its cognate E3 Ub ligases. In vitro and in vivo analyses of activity-reducing mutants of the yeast Ub-conjugating (Ubc) enzyme, Ubc7, demonstrated selective activation by one of its two cognate E3 ligases, Hrd1, but not by the other, Doa10. Supported by structural modeling of the RING:Ubc7∼Ub complex, these findings are consistent with a model whereby the E2∼Ub transition state depends on noncovalent interactions between helix α2 of Ubc7 and Ub that are differentially stabilized by the two E3 RING domains. 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