ClpX protein unfolding machine

Figure: Although the ClpX degradation machine is composed of six identical subinuts (here pictured in different colors), the structure exhibits quasi-2D symmetry, with only four of subunits able to bind ATP. The Xray structure corresponds to PDB accession code 3HWS

ClpX is an important member of the AAA+ family (ATPases Associated with diverse cellular Activities), which carries out protein `recycing' inside cells.  ClpX is a hexameric, ATP-powered protein unfolding machine that often functions in complex with a protease (ClpP) to degrade misfolded or nonfunctional proteins. Recently, Xray crystal structures of E. Coli ClpX were solved by Professor Sauer's group at the Massachusetts Institute of Technology, which provided a first snapshot of how the ClpX enzyme might act to denature folded proteins. Subtle differences in the ATP/ADP-dependent conformations of the six sububits of ClpX suggest that the binding of ATP, or the release of hydrolysis products (ADP+Pi) drives the motion of loops facing the central pore. The motion `threads' the protein substrate through the ClpX pore, mush like pulling a thread  through the eye of a needle. Recently solved Xray structures ( Glynn et al.,  Cell 2009) show the ClpX machine in different chemical states, and with different mutations.  In collaboration with Professor Sauer's goup at MIT,  we use molecular dynamics simulations to bias conformational transitions between different states of ClpX to understand how the ATP-dependent conformational changes in the subunits can pull the protein through the central pore.