PhoP-PhoQ: Difference between revisions
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'''PhoP-PhoQ''' is a two component regulatory system found in some gram-negative bacteria such as ''Escherichia Coli'', ''Salmonella Typhimurium'', and ''Yersinia Pestis''. In a classic two component regulatory system, there exists a sensor kinase and a response regulator. In the phoP-phoQ system, phoQ acts as the sensor kinase and phoP acts as the response regulator. The purpose of this signal transduction system in bacteria is to modify cellular output in response to environmental signals. In response to particular environmental stimuli, such as a low [Mg<sup>2+</sup>], the sensor kinase, phoQ autophosphorylates. Phosphorylated phoQ then transphosphorylates the response regulator, phoP, which in turn binds DNA and | '''PhoP-PhoQ''' is a two component regulatory system found in some gram-negative bacteria such as ''Escherichia Coli'', ''Salmonella Typhimurium'', and ''Yersinia Pestis''. In a classic two component regulatory system, there exists a sensor kinase and a response regulator. In the phoP-phoQ system, phoQ acts as the sensor kinase and phoP acts as the response regulator. The purpose of this signal transduction system in bacteria is to modify cellular output in response to environmental signals. In response to particular environmental stimuli, such as a low [Mg<sup>2+</sup>], the sensor kinase, phoQ autophosphorylates. Phosphorylated phoQ then transphosphorylates the response regulator, phoP, which in turn binds DNA and modulates transcription. | ||
<StructureSection load='2pl1' size='500' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''> | <StructureSection load='2pl1' size='500' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''> | ||
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E. coli phoP is a 223 residue protein containing a 120-residue regulatory domain joined by a 5-residue linker to a 98 residue c-terminal DNA binding effector domain. At a conserved Asp residue, the regulatory domain can be modified by a phosphoryl group from the protein kinase function of phoQ. Phosphorylation of the regulatory domain modulates the activity of the effector domain to bind DNA and regulate transcription. Phosphorylated, or "activated" phoP binds to "phoP boxes" on bacterial DNA, which consist of two direct hexanucleotide repeats separated by a five nucleotide spacer located at the -35 position: | E. coli phoP is a 223 residue protein containing a 120-residue regulatory domain joined by a 5-residue linker to a 98 residue c-terminal DNA binding effector domain. At a conserved Asp residue, the regulatory domain can be modified by a phosphoryl group from the protein kinase function of phoQ. Phosphorylation of the regulatory domain modulates the activity of the effector domain to bind DNA and regulate transcription. Phosphorylated, or "activated" phoP binds to "phoP boxes" on bacterial DNA, which consist of two direct hexanucleotide repeats separated by a five nucleotide spacer located at the -35 position: | ||
(T/G)GTTTA | |||
===Dimerization of Activated phoP=== | ===Dimerization of Activated phoP=== | ||
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In this structure, <scene name='Sandbox_Reserved_344/P-analog/1'>Beryllofluoride</scene> (BeF<sub>3</sub><sup>-</sup>) is used as a phosphoryl analog to induce the active state conformation. There are numerous bonds that form as a result of BeF<sub>3</sub><sup>-</sup> coordination. F<sub>1</sub> of BeF<sub>3</sub><sup>-</sup> helps satisfy the octahedral coordination of a present active site <scene name='PhoP-PhoQ/Mg-f1/ | In this structure, <scene name='Sandbox_Reserved_344/P-analog/1'>Beryllofluoride</scene> (BeF<sub>3</sub><sup>-</sup>) is used as a phosphoryl analog to induce the active state conformation. There are numerous bonds that form as a result of BeF<sub>3</sub><sup>-</sup> coordination. F<sub>1</sub> of BeF<sub>3</sub><sup>-</sup> helps satisfy the octahedral coordination of a present active site <scene name='PhoP-PhoQ/Mg-f1/4'>Mg</scene><sup>2+</sup>. The conserved active site lysine, <scene name='PhoP-PhoQ/Lys101-f3/2'>Lys101</scene>, forms important intramolecular and intermolecular salt bridges, one of which is with F<sub>3</sub> of BeF<sub>3</sub><sup>-</sup>. A conserved "switch residue" <scene name='PhoP-PhoQ/Thr79-f2/2'>Thr79</scene>, involved in the activation of all response regulators, forms a H-bond with F<sub>2</sub> of BeF<sub>3</sub><sup>-</sup>. F<sub>2</sub> of BeF<sub>3</sub><sup>-</sup> also forms a H-bond with the backbone nitrogen atom of <scene name='PhoP-PhoQ/Gly53-f2/3'>Gly53</scene>. | ||
</StructureSection> | </StructureSection> | ||
===PhoP-PhoQ and Virulence=== | ===PhoP-PhoQ and Virulence=== | ||