Introduction
PhoP is the response regulator of the PhoP/PhoR two-component regulatory system in Mycobacterium tuberculosis. It controls genes involved in virulence, lipid biosynthesis, and cell-wall remodeling. The molecular basis of how PhoP recognizes its target promoters was clarified by the crystal structure of the PhoP DNA-binding domain bound to its cognate DNA sequence (PDB ID: 3R0J).
The structure reveals that PhoP binds DNA as a symmetric dimer through a classical helix–turn–helix (HTH) motif. The recognition helix inserts deeply into the major groove, forming base-specific hydrogen bonds that explain promoter selectivity. Additional interactions arise from a winged-helix region that stabilizes the complex through minor-groove contacts. Mutational analyses demonstrate that substitutions of DNA-contacting residues significantly impair binding and transcriptional regulation. Together, the 3R0J structure provides a detailed molecular explanation for PhoP-mediated gene control in M. tuberculosis.
Function
- Response regulator controlling virulence and lipid metabolism genes
- Activated under environmental stress signals
- Works with sensor kinase PhoR
Relevance
PhoP regulates several virulence-associated pathways in M. tuberculosis. Structural defects in PhoP lead to attenuation, making it important for understanding TB pathogenesis and drug-target exploration.
Structural Highlights
1. Overall PhoP–DNA Complex
2. DNA-Binding Interface
3. Close-up of Key Residues
Methods
- Structure: PDB ID 3R0J
- Software: PyMOL
- Images were generated using ray-traced rendering (2400×1800 resolution)
- Scenes created using SAT on Proteopedia
References
- Structural basis of DNA sequence recognition by the response regulator PhoP in Mycobacterium tuberculosis. (add full citation)
