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''[http://en.wikipedia.org/wiki/Escherichia_coli], ''Salmonella enterica'' Typhi[http://en.wikipedia.org/wiki/Salmonella_enterica], and ''Yersinia pestis''[http://en.wikipedia.org/wiki/Yersinia_pestis]. In a classic two component regulatory system, there exists a sensor kinase and a response regulator<ref name=Hoch>PMID:10745001</ref>. 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.<ref name=Hoch>PMID:10745001</ref> For more details see [[PhoP Regulatory Domain]]. | '''PhoP-PhoQ''' is a two component regulatory system found in some gram-negative bacteria such as ''Escherichia coli''[http://en.wikipedia.org/wiki/Escherichia_coli], ''Salmonella enterica'' Typhi[http://en.wikipedia.org/wiki/Salmonella_enterica], and ''Yersinia pestis''[http://en.wikipedia.org/wiki/Yersinia_pestis]. In a classic two component regulatory system, there exists a sensor kinase and a response regulator<ref name=Hoch>PMID:10745001</ref>. 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.<ref name=Hoch>PMID:10745001</ref> For more details see [[PhoP Regulatory Domain]]. | ||
===PhoP: The Response Regulator=== | ===PhoP: The Response Regulator=== | ||
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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.<ref name=Bachhawat>PMID:17545283</ref> At a conserved Asp residue (<scene name='PhoP-PhoQ/Asp51-bef3/1'>Asp51 in this case</scene>), 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.<ref name=Bachhawat>PMID:17545283</ref>: | ''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.<ref name=Bachhawat>PMID:17545283</ref> At a conserved Asp residue (<scene name='PhoP-PhoQ/Asp51-bef3/1'>Asp51 in this case</scene>), 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.<ref name=Bachhawat>PMID:17545283</ref>: | ||
(T/G)GTTTA | (T/G)GTTTA | ||
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Spontaneous dimerization of the unactivated phoP regulatory domain can be observed in vitro, but is likely due to high concentration of the protein and may not occur in vivo. Although the dimerization of the unactivated phoP regulatory domain results in a homodimer similar to the activated homodimer, it is significantly less stable. Activation by the phosphoryl group helps to stabilize the <scene name='Sandbox_Reserved_344/Dimerization_surface/1'>α-4 helix, β-5 sheet and α-5 helix face</scene> dimerization interphase. Without the phosphoryl group, the two monomers dimerize in an asymmetric fashion that lends to molecular instability. | Spontaneous dimerization of the unactivated phoP regulatory domain can be observed in vitro, but is likely due to high concentration of the protein and may not occur in vivo. Although the dimerization of the unactivated phoP regulatory domain results in a homodimer similar to the activated homodimer, it is significantly less stable. Activation by the phosphoryl group helps to stabilize the <scene name='Sandbox_Reserved_344/Dimerization_surface/1'>α-4 helix, β-5 sheet and α-5 helix face</scene> dimerization interphase. Without the phosphoryl group, the two monomers dimerize in an asymmetric fashion that lends to molecular instability. | ||
===PhoP-PhoQ and Virulence=== | ===PhoP-PhoQ and Virulence=== | ||
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Two component regulatory systems such as phoP-phoQ are obviously an attractive target for future antimicrobial drugs. If the phoP-phoQ can be altered to a dysfunctional state, the relevant bacteria would have decreased pathogenicity and increased suceptibility to nonspecific immune defense. | Two component regulatory systems such as phoP-phoQ are obviously an attractive target for future antimicrobial drugs. If the phoP-phoQ can be altered to a dysfunctional state, the relevant bacteria would have decreased pathogenicity and increased suceptibility to nonspecific immune defense. | ||
</StructureSection> | |||
== 3D Structures of PhoP-PhoQ== | == 3D Structures of PhoP-PhoQ== | ||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
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**[[3cgz]] - StPhoQ catalytic domain<br /> | **[[3cgz]] - StPhoQ catalytic domain<br /> | ||
**[[1yax]] - StPhoQ sensor domain (mutant)<br /> | **[[1yax]] - StPhoQ sensor domain (mutant)<br /> | ||
**[[3bq8]] – EcPhoQ<br /> | **[[3bq8]], [[6a8u]] – EcPhoQ sensor domain<br /> | ||
**[[3bqa]] – EcPhoQ (mutant)<br /> | **[[3bqa]], [[6a8v]] – EcPhoQ sensor domain (mutant)<br /> | ||
**[[1id0]] – EcPhoQ kinase domain | **[[1id0]] – EcPhoQ kinase domain<br /> | ||
**[[4uey]] - PhoQ periplasmic domain (mutant) – ''Salmonella enterica''<br /> | |||
}} | }} | ||
===References=== | ===References=== | ||