Distinct static and dynamic interactions control ATPase-Peptidase communication in a AAA plus protease

In the CIpXP proteolytic machine, CIpX uses the energy of ATP hydrolysis to unfold protein substrates and translocate them through a central pore and into the degradation chamber of CIpP. Here, we demonstrate a bipartite system of CIpX-CIpP interactions that serves multiple functional roles. High-affinity contacts between six loops near the periphery of the hexameric CIpX ring and a CIpP ring establish correct positioning and increase degradation activity but are insensitive to nucleotide state. These static peripheral interactions maintain a stable CIpXP complex, while other parts of this machine change conformation hundreds of times per minute. By contrast, relatively weak axial contacts between loops at the bottom of the CIpX central channel and N-terminal loops of CIpP vary dynamically with the nucleotide state of individual CIpX subunits, control ATP-hydrolysis rates, and facilitate efficient protein unfolding. Thus, discrete static and dynamic interactions mediate binding and communication between CIpX and CIpP.