Research Highlights

Regulatory role of PhoP

doi:10.1038/nindia.2009.354 Published online 22 December 2009

Researchers have studied relative orientation of protein monomers in the DNA binding transcription regulator 'PhoP' in Mycobacterium tuberculosis. Their research raises the possibility that PhoP might adopt various modes to bind to a vast array of genes and be able to both activate or suppress the process of transcription1.

PhoP is the DNA binding transcription factor of the PhoP-PhoR two-protein regulatory system and is a key regulator for growth and virulence of the tubercle bacillus.

Global gene expression profiling indicates that more than 110 genes are regulated by PhoP. To identify which genetic determinants PhoP regulates, the researchers showed that the protein recognizes a 23-base pair sequence of the phoP upstream region comprising two adjacent direct repeat motifs believed to promote transcription regulation.

PhoP has a phosphorylation domain at its amino-terminal half and a DNA-binding domain at its carboxy-terminal half. The researchers have shown that DNA binding involves two monomeric PhoP molecules on the target DNA. They also show that formation of a DNA-protein complex is dependent on conserved terminal adenines of the repeat sequences, which in turn suggests a novel DNA binding arrangement of the protein.

Although other known response regulators like PhoB and FixJ dimerize upon phosphorylation, this research demonstrates that PhoP dimerization can also be stimulated by DNA binding.


References

  1. Gupta, S. et al. Mycobacterium tuberculosis PhoP recognizes two adjacent direct-repeat sequences to form head-to-head dimers. J. Bacteriol. 191, 7466-7476 (2009) | Article | PubMed |