Computational Advances in Structural Biology

Abstract:

Some bacterial AAA+ proteases are composed of an ATPase that perform unfolding (such as ClpC, ClpA or ClpX) and an associated peptidase (such as ClpP). They are proteolytic machines crucial for bacterial heat or oxidative stress resistance as well as for virulence. ClpC in particular cooperates with specific adapter proteins such as MecA, which delivers damaged or aggregated substrates to the ClpC/ClpP proteolytic machine and concomitantly boosts ClpC ATPase activity. Here, we present the cryo EM structure of the MecA/ClpC/ClpP complex from the major pathogen Staphylococcus aureus and, in combination with biochemical assays and mutagenesis, we show possible ways of fine tuning this proteolytic machine.