From DrugPedia: A Wikipedia for Drug discovery

Revision as of 17:15, 26 January 2010

General

Heat shock proteins (HSP) are a class of functionally related proteins whose expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all living organisms, from bacteria to humans.

During stationary growth or in vitro conditions mimicking relevant aspects of latency, the HspX protein (Rv2031c) is specifically upregulated by Mycobacterium tuberculosis. Gamma interferon responses to HspX are significantly higher in M.tuberculosis-exposed individuals than in M. tuberculosis-unexposed BCG vaccinees.

The 16-kDa protein, an alpha -crystallin homologue, is one of the most abundant proteins in stationary-phase Mycobacterium tuberculosis. Here, transcription and translation of the hspX gene, which encodes the 16-kDa protein, have been investigated by Northern blotting analysis, primer extension, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a microaerophilic stationary-phase model. Two transcripts of about 2.5 and 1.1 kb were demonstrated by Northern blot analysis and hybridized to the hspX gene probe. Primer extension analysis revealed that the transcription start site is located 33 nucleotides upstream of the hspX gene start codon. The cellular level of the hspX mRNA was maximum in log-phase bacilli and was markedly reduced after 20 days in unagitated culture, when the organisms had entered the stationary phase. In contrast to the high level of hspX mRNA in log-phase bacilli, 16-kDa protein synthesis was low in log-phase bacteria and rose to its maximum after 20 days. In both log-phase and stationary-phase bacteria the mRNA was unstable, with a half-life of 2 min, which indicated that the transcript stability was growth rate independent and not a general means for controlling the gene expression.These data suggest that the regulation of hspX expression during entry into and maintenance of stationary phase involves translation initiation efficiency and protein stability as potential mechanisms.

The RT-PCR results have show that hspX (encoding the {alpha}-crystallin antigen Acr) were expressed throughout the cultivation period.

Protein Sequence

>Rv2031c, TB.seq 2278499:2278930 MW:16228 MATTLPVQRHPRSLFPEFSELFAAFPSFAGLRPTFDTRLMRLEDEMKEGRYEVRAELPGVDPDKDVDIMVRDGQLTIKAE RTEQKDFDGRSEFAYGSFVRTVSLPVGADEDDIKATYDKGILTVSVAVSEGKPTEKHIQIRSTN

Human Homologue Blast Result