the htra-like serine protease pepd interacts with and modulates the mycobacterium tuberculosis 35-kda antigen outer envelope protein的htra-like丝氨酸蛋白酶pepd与结核分枝杆菌,调节35-kda外层包膜蛋白抗原.pdfVIP

The HtrA-Like Serine Protease PepD Interacts with and Modulates the Mycobacterium tuberculosis 35-kDa Antigen Outer Envelope Protein Mark J. White1,2, John P. Savaryn1,3, Daniel J. Bretl1,2, Hongjun He1,2, Renee M. Penoske1,2, Scott S. Terhune1,3, Thomas C. Zahrt1,2* 1 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 2 Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 3 Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America Abstract Mycobacterium tuberculosis remains a significant global health concern largely due to its ability to persist for extended periods within the granuloma of the host. While residing within the granuloma, the tubercle bacilli are likely to be exposed to stress that can result in formation of aberrant proteins with altered structures. Bacteria encode stress responsive determinants such as proteases and chaperones to deal with misfolded or unfolded proteins. pepD encodes an HtrA-like serine protease and is thought to process proteins altered following exposure of M. tuberculosis to extra-cytoplasmic stress. PepD functions both as a protease and chaperone in vitro, and is required for aspects of M. tuberculosis virulence in vivo. pepD is directly regulated by the stress-responsive two-component signal transduction system MprAB and indirectly by extracytoplasmic function (ECF) sigma factor SigE. Loss of PepD also impacts expression of other stress-responsive determinants in M. tuberculosis. To further understand the role of PepD in stress adaptation by M. tuberculosis, a proteomics approach was taken to identify binding proteins and possible substrates of this protei