five mechanisms of manipulation by bacterial effectors a ubiquitous theme五个机制的操纵细菌效应器无处不在的主题.pdfVIP

Pearls Five Mechanisms of Manipulation by Bacterial Effectors: A Ubiquitous Theme David M. Anderson1,2, Dara W. Frank1,2* 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 Ubiquitin, a highly conserved polypeptide of 76 amino acids, C-terminal NEL domains upon substrate recognition and before participates in a vast range of eukaryotic cell processes through its catalysis [7,12–14]. Collectively, these mimics are profound role as a reversible post-translational modifier (see review [1], examples of convergent evolution and the utilization of different Figure 1A). Such extensive utilization of a single protein within a strategies for solving a similar biological problem. host cell lends itself to be an ideal target for microbial manipulation. Host-pathogen co-evolution has endowed present- Deubiquitylation day pathogens with an ever-expanding repertoire of proteins that function to modulate this system. The majority of these proteins Many bacteria synthesize effectors that interfere with host are effectors of type III secretion (T3S) or type IV secretion (T4S) ubiquitylation by mimicking host deubiquitylases (DUBs). Eukary- pathways, which are major virulence determinants of many Gram- otic DUBs exhibit exquisite substrate specificity and are important negative pathogens [2,3]. This review is focused on five distinct regulatory components within the host ubiquitin system [15]. mechanisms in which secreted bacterial effector proteins exploit Bacterial DUBs are generally modele