Molecular basis of ParA ATPase activation by the CTPase ParB during bacterial chromosome segregation

DNA segregation by bacterial ParAB S systems is mediated by transient tethering interactions between nucleoid-bound dimers of the ATPase ParA and centromere ( parS )-associated complexes of the clamp-forming CTPase ParB. The lifetime of these interactions is limited by the ParB-dependent activation of ParA ATPase activity. Here, we elucidate the functional interplay between ParA and ParB in the model bacterium Myxococcus xanthus . We demonstrate that the N-terminal ParA-binding motif of ParB associates with a conserved bipartite binding pocket at the ParA dimer interface, in a manner dependent on ParB clamp closure. Moreover, we show that ParB and non-specific DNA interact cooperatively with ParA and synergistically induce structural changes at its Walker A and Walker B motifs that correlate with the activation of ParA ATPase activity. These results advance our understanding of the mechanism underlying DNA transport by the ParAB S system and may help to unravel the mode of action of related cargo-positioning systems.