Fig. 6.

A proposed model for the activation of Ubc7 by the RING domains of Doa10 and Hrd1. Ub bound to Ubc7 at the active site is largely in a loose (open) conformation. Both Doa10 and Hrd1 RING promote the closed transition state conformation by stabilizing noncovalent interaction of Ub with helix α2. The Hrd1 RING domain can form additional interactions that stabilize the closed conformation and thus can overcome compromised helix α2:Ub interactions. Arrows indicate the direction of nucleophilic attack by an acceptor Lys. Joined arrowheads indicate the degree to which the donor Ub is free to wobble.