PhoP-PhoQ - Revision history

Michal Harel at 07:30, 22 September 2020

2020-09-22T07:30:43Z

←Older revision		Revision as of 07:30, 22 September 2020
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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]], [[~~6abu~~]] – EcPhoQ sensor domain<br />	+	**[[3bq8]], [[6a8u]] – EcPhoQ sensor domain<br />
-	**[[3bqa]], [[~~6abv~~]] – EcPhoQ sensor domain (mutant)<br />	+	**[[3bqa]], [[6a8v]] – EcPhoQ sensor domain (mutant)<br />
	**[[1id0]] – EcPhoQ kinase domain<br />		**[[1id0]] – EcPhoQ kinase domain<br />
	**[[4uey]] - PhoQ periplasmic domain (mutant) – ''Salmonella enterica''<br />		**[[4uey]] - PhoQ periplasmic domain (mutant) – ''Salmonella enterica''<br />

Michal Harel at 08:16, 17 November 2019

2019-11-17T08:16:35Z

←Older revision		Revision as of 08:16, 17 November 2019
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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]], [[6abu]] – EcPhoQ sensor domain<br />
-	**[[3bqa]] – EcPhoQ (mutant)<br />	+	**[[3bqa]], [[6abv]] – EcPhoQ sensor domain (mutant)<br />
	**[[1id0]] – EcPhoQ kinase domain<br />		**[[1id0]] – EcPhoQ kinase domain<br />
	**[[4uey]] - PhoQ periplasmic domain (mutant) – ''Salmonella enterica''<br />		**[[4uey]] - PhoQ periplasmic domain (mutant) – ''Salmonella enterica''<br />

Michal Harel at 09:40, 31 August 2017

2017-08-31T09:40:29Z

←Older revision		Revision as of 09:40, 31 August 2017
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	**[[3bq8]] – EcPhoQ<br />		**[[3bq8]] – EcPhoQ<br />
	**[[3bqa]] – EcPhoQ (mutant)<br />		**[[3bqa]] – EcPhoQ (mutant)<br />
-	**[[1id0]] – EcPhoQ kinase domain	+	**[[1id0]] – EcPhoQ kinase domain<br />
		+	**[[4uey]] - PhoQ periplasmic domain (mutant) – ''Salmonella enterica''<br />
	}}		}}
	===References===		===References===

Michal Harel at 08:37, 23 June 2016

2016-06-23T08:37:35Z

←Older revision		Revision as of 08:37, 23 June 2016
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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.
-	~~</StructureSection>~~	+
	===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}}

Michal Harel at 08:36, 23 June 2016

2016-06-23T08:36:00Z

←Older revision		Revision as of 08:36, 23 June 2016
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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]].

-
-	{{TOC limit\|limit=2}}
	===PhoP: The Response Regulator===		===PhoP: The Response Regulator===

Michal Harel at 12:05, 17 February 2016

2016-02-17T12:05:02Z

←Older revision		Revision as of 12:05, 17 February 2016
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-	<StructureSection load='2pl1' size='~~500~~' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''>	+	<StructureSection load='2pl1' size='350' side='right' caption='BeF activated PhoP domain of E. Coli complex with BeF4, Pt+2 (grey) and Mg+2 ions (PDB entry [[2pl1]])' scene=''>
	{{TOC limit\|limit=2}}		{{TOC limit\|limit=2}}

Alexander Berchansky at 09:25, 3 December 2014

2014-12-03T09:25:03Z

←Older revision		Revision as of 09:25, 3 December 2014
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-	~~{{STRUCTURE_3bq8\| PDB~~=~~3bq8 \| SIZE~~=~~400\| SCENE~~= \|right~~\|CAPTION~~=''E. ~~coli'' Se-Met PhoQ complex with Ni+2 and acetic acid,~~ [[~~3bq8~~]] }}	+	<StructureSection load='2pl1' size='500' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''>
	{{TOC limit\|limit=2}}		{{TOC limit\|limit=2}}

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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]].

-	~~<StructureSection load='2pl1' size='500' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''>~~	+
	{{TOC limit\|limit=2}}		{{TOC limit\|limit=2}}
	===PhoP: The Response Regulator===		===PhoP: The Response Regulator===

Michal Harel at 07:08, 3 December 2014

2014-12-03T07:08:46Z

←Older revision		Revision as of 07:08, 3 December 2014
Line 47:		Line 47:
	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.
	== 3D Structures of PhoP-PhoQ==		== 3D Structures of PhoP-PhoQ==
		+	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
		+	{{#tree:id=OrganizedByTopic\|openlevels=0\|

-	~~===~~PhoP~~===~~	+	*PhoP

-	[[3r0j]] – MtPhoP – ''Mycobacterium tuberculosis''<br />	+	**[[3r0j]] – MtPhoP – ''Mycobacterium tuberculosis''<br />
-	[[2pmu]] – MtPhoP DNA-binding domain<br />	+	**[[2pmu]] – MtPhoP DNA-binding domain<br />
-	[[2pkx]] – EcPhoP regulatory domain (mutant) – ''Escherichia coli''<br />	+	**[[2pkx]] – EcPhoP regulatory domain (mutant) – ''Escherichia coli''<br />
-	[[2pl1]] - EcPhoP regulatory domain (mutant) + BeF3<br />	+	**[[2pl1]] - EcPhoP regulatory domain (mutant) + BeF3<br />
-	[[1mvo]] – PhoP N terminal – ''Bacillus subtilis''	+	**[[1mvo]] – PhoP N terminal – ''Bacillus subtilis''

-	~~===~~PhoQ~~===~~	+	*PhoQ
-		+
-	~~[[3cgy]] – StPhoQ catalytic domain + radicicol – ''Salmonella typhimurium''<br />~~	+
-	~~[[3cgz]] - StPhoQ catalytic domain<br />~~	+
-	~~[[1yax]] - StPhoQ sensor domain (mutant)<br />~~	+
-	~~[[3bq8]] – EcPhoQ<br />~~	+
-	~~[[3bqa]] – EcPhoQ (mutant)<br />~~	+
-	~~[[1id0]] – EcPhoQ kinase domain~~	+

		+	**[[3cgy]] – StPhoQ catalytic domain + radicicol – ''Salmonella typhimurium''<br />
		+	**[[3cgz]] - StPhoQ catalytic domain<br />
		+	**[[1yax]] - StPhoQ sensor domain (mutant)<br />
		+	**[[3bq8]] – EcPhoQ<br />
		+	**[[3bqa]] – EcPhoQ (mutant)<br />
		+	**[[1id0]] – EcPhoQ kinase domain
		+	}}
	===References===		===References===

Michal Harel at 07:48, 1 February 2012

2012-02-01T07:48:41Z

←Older revision		Revision as of 07:48, 1 February 2012
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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>	+	'''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]].

	<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=''>

Andrew Brockfield at 23:02, 15 November 2011

2011-11-15T23:02:18Z

←Older revision		Revision as of 23:02, 15 November 2011
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	Pathogenic bacteria seldom express virulence genes constitutively, they instead need to be able to express the correct virulence genes in the correct environment. Not all virulence factors confer a selective advantage to the microbe at the same stage of infection. Thus, it is the job of the phoP-phoQ system to modulate virulence gene expression according to the cellular micro-environment.<ref name=Hoch>PMID:10745001</ref>		Pathogenic bacteria seldom express virulence genes constitutively, they instead need to be able to express the correct virulence genes in the correct environment. Not all virulence factors confer a selective advantage to the microbe at the same stage of infection. Thus, it is the job of the phoP-phoQ system to modulate virulence gene expression according to the cellular micro-environment.<ref name=Hoch>PMID:10745001</ref>

-	A particular and well studied example of this is the role of [Mg<sup>2+</sup.] in ''Salmonella enterica'' Typhi virulence. In response to low [Mg<sup>2+</sup>], such as would be found inside a macrophage phagosome, phoQ autophosphorylates and transphorphorylates phoP. PhoP then binds to the bacterial DNA and simultaneously activates the expression of pags (phoP activated genes) and represses the expression of prgs (phoP repressed genes). Among the gene products of pags are proteins necessary to survive inside the macrophage, a critical stage of ''Salmonella enterica'' Typphi pathogenesis. Among the gene products of prgs are proteins necessary for invasion and infection of the host, which are less important once in a host macrophage's phagosome.	+	A particular and well studied example of this is the role of [Mg<sup>2+</sup>] in ''Salmonella enterica'' Typhi virulence. In response to low [Mg<sup>2+</sup>], such as would be found inside a macrophage phagosome, phoQ autophosphorylates and transphorphorylates phoP. PhoP then binds to the bacterial DNA and simultaneously activates the expression of pags (phoP activated genes) and represses the expression of prgs (phoP repressed genes). Among the gene products of pags are proteins necessary to survive inside the macrophage, a critical stage of ''Salmonella enterica'' Typphi pathogenesis. Among the gene products of prgs are proteins necessary for invasion and infection of the host, which are less important once in a host macrophage's phagosome.

	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.