12 Modifications of small GTP-binding proteins by bacterial protein toxins

Abstract

Publisher Summary This chapter focuses on the modifications of small GTP-binding proteins by bacterial protein toxins. Rho GTP-binding proteins belong to the p21 Ras superfamily which is divided into five main branches: Ras, Rho, Rab, Sar/Arf and Ran. Such as other small GTPases Rho are molecular switches playing the role of intracellular timers in signal transduction cascades. Bound to GTP they are in their active form and upon hydrolysis of the nucleotide into GDP they return back to their inactive state. Their ability to hydrolyze GTP into GDP, in conjunction with a helper protein (GTPase-activating-protein GAP), has led to them being named small GTPases. Members of the Rho subfamily of GTPases are clearly preferred targets of several bacterial toxins and virulence factors that can manipulate them to either activate or inhibit these proteins permanently. The discovery of Clostridium botulinurn exoenzyme C3 has led to the elucidation of the role of the Rho GTPases in the control of the cytoskeleton organization therefore allowing one to understand the molecular mechanism of large clostridial cytotoxins together with the discovery of a new covalent modification of target proteins by bacterial toxins.