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SUMMARY Pathogenic bacteria commonly deploy enzymes to promote virulence. in the

SUMMARY Pathogenic bacteria commonly deploy enzymes to promote virulence. in the sequence. Deamidation of target host proteins can disrupt host signaling and downstream processes by either activating or inactivating the target. Despite the subtlety of this modification it has been CCT241533 shown to cause dramatic context-dependent effects on host cells. Several crystal structures of bacterial deamidases have been solved. All are members of the papain-like superfamily and display a cysteine-based catalytic triad. However these proteins form unique structural subfamilies and feature combinations of modular domains of various functions. Based on the diverse pathogens that use deamidation as a mechanism to promote virulence and the recent identification of multiple deamidases it is clear that this enzymatic activity is usually emerging as an important and common feature in bacterial pathogenesis. INTRODUCTION Many bacterial pathogens use diverse suites of virulence factors to contribute to pathogenicity. These virulence factors include toxins and type III effectors which are proteins injected into host cells via specialized type III secretion systems. Effectors often modify eukaryotic host target proteins with posttranslational modifications that alter normal cellular function. Commonly explained posttranslational modifications utilized by effectors include ubiquitination acetylation and AMPylation (1-3). Recently enzymatic deamidation has emerged as a common posttranslational modification utilized by a broad range of bacterial pathogens of both plants and animals to alter the functions of host proteins. Deamidation is the replacement of an amide group with a carboxylate group (Fig. 1). Therefore it converts glutamine and asparagine to glutamic acid and aspartic acid respectively. This irreversible amino acid conversion results in CCT241533 an increase of approximately 1 Da in the mass of the target protein an increase in the unfavorable charge of the target protein and the release of ammonia. Nonspecific deamidation can occur spontaneously as proteins age and are degraded (4). In contrast specific enzymatic deamidation can regulate normal cellular functions such as chemotaxis and protein turnover in Rabbit polyclonal to NFKBIE. prokaryotes or disrupt eukaryotic host cell function during contamination (5 6 Here we focus on deamidases that contribute to bacterial virulence. Fig 1 Schematic representation of enzymatic deamidation in proteins. Deamidases take action on specific residues in the target protein. For all those currently analyzed bacterial virulence factors the targets of deamidation are glutamine side chains which are converted … The topic of this review is the six currently known families of bacterial virulence factors that use deamidation to modulate host functions during contamination (Table 1). Cytotoxic necrotizing factors (CNFs) are a family of deamidases from (CNF1 -2 and -3) and (CNFY). The CNFs target a glutamine residue (either Gln63 or Gln61) in the switch II CCT241533 domain name of GTPase proteins that is critical for function (7 8 Deamidation of this glutamine prospects to constitutive activation of the target GTPases resulting in cytoskeletal rearrangements. Reorganization of the actin CCT241533 cytoskeleton is usually one mechanism used by invasive bacteria to promote entry into host cells (9 10 BLF1 is usually a toxin from that is lethal to mice and tissue culture cells (11). BLF1 inhibits host protein synthesis via deamidation of eIF4A (11). VopC is usually a type III effector from that deamidates and constitutively activates small GTPases (12). toxin (PMT) is the major virulence factor of that dampens host immune responses by deamidating UBC13 and disrupting the TRAF6-mediated signaling pathway (15). We evaluate the details of each of these six families specifically with respect to their three-dimensional structures and the impact that deamidation has on the functions of their host target proteins. We conclude that deamidation as a nonreversible modification is likely an “all or nothing” virulence switch to alter diverse cellular functions across diverse CCT241533 pathosystems. Table 1 Bacterial virulence factors that use deamidation to modify host proteins CYTOTOXIC. CCT241533