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PMID:18479146

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Citation

Mohamedmohaideen, NN, Palaninathan, SK, Morin, PM, Williams, BJ, Braunstein, M, Tichy, SE, Locker, J, Russell, DH, Jacobs, WR Jr and Sacchettini, JC (2008) Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis. Biochemistry 47:6092-102

Abstract

The high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis ( Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 A resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb.

Links

PubMed Online version:10.1021/bi701929m

Keywords

Animals; Bacterial Proteins/metabolism; Escherichia coli/metabolism; Gene Amplification; Heat-Shock Proteins/metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Mutagenesis, Site-Directed; Mycobacterium tuberculosis/enzymology; Mycobacterium tuberculosis/genetics; Mycobacterium tuberculosis/metabolism; Mycobacterium tuberculosis/pathogenicity; Periplasmic Proteins/metabolism; Polymerase Chain Reaction; Restriction Mapping; Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism; Tuberculosis/enzymology; Virulence

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MYCTU:PEPD

involved_in

GO:0030163: protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MYCTU:PEPD

enables

GO:0008236: serine-type peptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MYCTU:O53896

enables

GO:0008236: serine-type peptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MYCTU:O53896

involved_in

GO:0009405: pathogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MYCTU:O53896

involved_in

GO:0030163: protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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