Helix Unfolding/Refolding Characterizes the Functional Dynamics of Staphylococcus aureus Clp Protease

• DOI: 10.1074/jbc.m113.452714
• Publication Date: 2013-04-27T00:13:58Z
• Authors: Fei Ye; Jie Zhang; Hongchuan Liu; Rolf Hilgenfeld; Ruihan Zhang; Xiangqian Kong; Lianchun Li; Junyan Lu; Xinlei Zhang; Donghai Li; Hualiang Jiang; Cai-Guang Yang; Cheng Luo
• Keywords: Helix (gastropod); Dynamics

The ATP-dependent Clp protease (ClpP) plays an essential role not only in the control of protein quality but also regulation bacterial pathogen virulence, making it attractive target for antibacterial treatment. We have previously determined crystal structures Staphylococcus aureus ClpP (SaClpP) two different states, extended and compressed. To investigate dynamic switching between these we performed a series molecular dynamics simulations. During structural transition, long straight helix E SaClpP monomer underwent unfolding/refolding process, resulting kinked very similar to that compressed monomer. As stable intermediate simulation, compact state was suggested subsequently identified x-ray crystallographic experiment. Our combined studies Ala(140) acted as "hinge" during transition Glu(137) stabilizing state. Overall, this study provides insights into mechanism functional conformation changes SaClpP. Given highly conserved sequences proteins among species, findings potentially reflect process shared whole family general thus aid better understand principles assembly function.