Insights into the ubiquitin transfer cascade catalyzed by the <i>Legionella</i> effector SidC.

Abstract

The causative agent of Legionnaires' disease, <i>Legionella pneumophila</i>, delivers more than 330 virulent effectors to its host to establish an intracellular membrane-bound organelle called the <i>Legionella</i> containing vacuole. Among the army of <i>Legionella</i> effectors, SidC and its paralog SdcA have been identified as novel bacterial ubiquitin (Ub) E3 ligases. To gain insight into the molecular mechanism of SidC/SdcA as Ub ligases, we determined the crystal structures of a binary complex of the N-terminal catalytic SNL domain of SdcA with its cognate E2 UbcH5C and a ternary complex consisting of the SNL domain of SidC with the Ub-linked E2 UbcH7. These two structures reveal the molecular determinants governing the Ub transfer cascade catalyzed by SidC. Together, our data support a common mechanism in the Ub transfer cascade in which the donor Ub is immobilized with its C-terminal tail locked in an extended conformation, priming the donor Ub for catalysis.