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The role of HtrA as a chaperone and protease in bacterial pathogenesis

By J.W. Marsh, S. Gloeckl, J.D.A. Tyndall and W.M. Huston

Abstract

HtrA (High Temperature Requirement A) is a critical stress response protease and chaperone for many bacteria. HtrA is a multitasking protein which can degrade unfolded proteins,\ud conduct specific proteolysis of some substrates for correct assembly, interact with substrates to ensure correct folding, assembly or localisation, and chaperone unfolded proteins. These functions are critical for the virulence of a number of bacterial pathogens, in some cases not simply due to the broad activities of HtrA in protection against the protein stress conditions which occur during virulence. But also due to the role of HtrA in either specific proteolysis or assembly of key protein substrates which function directly in virulence. Remarkably, these\ud activities are all conducted without any requirement for ATP. The biochemical mechanism of HtrA relies both on the chymotryptic serine protease active site as well as the presence of two PDZ (protein binding) domains. The mechanism is a unique combination of activation by\ud substrate motifs to alter the confirmation of the active site, and assembly into a multimeric complex which has enhanced degradation and may also act as a protective cage for proteins which are not degraded. The role of this protease in the pathogenesis of a number of bacteria\ud and the details of its distinctive biochemical activation and assembly mechanisms are discussed in this chapter

Topics: 060100 BIOCHEMISTRY AND CELL BIOLOGY, 060107 Enzymes, 060500 MICROBIOLOGY, 060502 Infectious Agents, HtrA, Protease, Chaperone, Bacteria
Publisher: Nova Publishers
Year: 2012
OAI identifier: oai:eprints.qut.edu.au:58495

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