High catalytic efficiency and resistance to denaturing in bacterial Rho GTPase-activating proteins
-
Yael Litvak
,
Rena Levin-Klein
Abstract
Several major bacterial pathogens use the type III secretion system (TTSS) to deliver virulence factors into host cells. Bacterial Rho GTPase activating proteins (RhoGAPs) comprise a remarkable family of type III secreted toxins that modulate cytoskeletal dynamics and manipulate cellular signaling pathways. We show that the RhoGAP activity of Salmonella SptP and Pseudomonas ExoS toxins is resistant to variations in the concentration of NaCl or MgCl2, unlike the known salt dependant nature of the activity of some eukaryotic GAPs such as p190, RanGAP and p120GAP. Furthermore, SptP-GAP and ExoS-GAP display full activity after treatment at 80°C or with 6 m urea, which suggests that these protein domains are capable of spontaneous folding into an active state following denaturing such as what might occur upon transit through the TTSS needle. We determined the catalytic activity of bacterial GAPs for Rac1, CDC42 and RhoA GTPases and found that ExoS, in addition to Yersinia YopE and Aeromonas AexT toxins, display higher catalytic efficiencies for Rac1 and CDC42 than the known eukaryotic GAPs, making them the most catalytically efficient RhoGAPs known. This study expands our knowledge of the mechanism of action of GAPs and of the ways bacteria mimic host activities and promote catalysis of eukaryotic signaling proteins.
©2011 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Publisher’s Note
- Publisher’s Note
- GENES AND NUCLEIC ACIDS
- Intermolecular interaction between a branching ribozyme and associated homing endonuclease mRNA
- Type V collagen-induced upregulation of capn2 (large subunit of m-calpain) gene expression and DNA fragmentation in 8701-BC breast cancer cells
- PROTEIN STRUCTURE AND FUNCTION
- High catalytic efficiency and resistance to denaturing in bacterial Rho GTPase-activating proteins
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- Cloning and functional analysis of the dpm2 and dpm3 genes from Trichoderma reesei expressed in a Saccharomyces cerevisiae dpm1Δ mutant strain
- MOLECULAR MEDICINE
- Increased expression of the multidrug resistance-associated protein 1 (MRP1) in kidney glomeruli of streptozotocin-induced diabetic rats
- CELL BIOLOGY AND SIGNALING
- Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R-/- mice
- PROTEOLYSIS
- Angiotensin I-converting enzyme (ACE) activity and expression in rat central nervous system after sleep deprivation
- Cathepsins S, B and L with aminopeptidases display β-secretase activity associated with the pathogenesis of Alzheimer’s disease
- The role of cathepsin E in terminal differentiation of keratinocytes
- Poliovirus 3C proteinase inhibition by organotelluranes
