Sandbox Reserved 344: Difference between revisions
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{{Template:Sandbox_Reserved_BCMB307}} | {{Template:Sandbox_Reserved_BCMB307}} | ||
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::::::'''THIS PAGE COPIED TO: '''[http://www.proteopedia.org/wiki/index.php/PhoP_Regulatory_Domain] | |||
{{STRUCTURE_2pl1|PDB=2pl1|SCENE=}} | {{STRUCTURE_2pl1|PDB=2pl1|SCENE=}} | ||
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=Introduction= | =Introduction= | ||
The response regulator PhoP from the OmpR/PhoB family of two-component systems is responsible for initiating the cellular response to the extracellular concentration of Mg<sup>2+</sup> of certain gram-negative bacteria such as ''Escherichia coli'' and ''Salmonella enterica''. A drop in Mg<sup>2+</sup> concentration is an indicator to the pathogenic bacteria that it has entered a host cell and needs to react correspondingly. The histidine protein kinase, PhoQ, spanning the inner membrane of the bacteria, senses the lowered Mg<sup>2+</sup> concentration and phosphorylates the cytosolic PhoP. PhoP forms a homodimer and sets a signal cascade in motion, affecting other two component signalling systems and directly regulating gene expression by binding to PhoP boxes on the DNA. PhoP consists of a regulatory domain and an effector domain. | |||
Gene regulation is achieved by the increased affinity of the homodimer to the PhoP box, a tandem repeat promoter. The response is organism specific but generally involves virulence and the survival in an environment with low Mg<sup>2+</sup> concentration. <ref name = "Bachh2007"> PMID:17545283</ref><ref name = "Groisman"> PMID:11222580</ref> | |||
=Structure= | =Structure= | ||
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:Phosphorylation of the regulatory domain stabilizes dimer formation. <ref name = "Bachh2007"/> | :Phosphorylation of the regulatory domain stabilizes dimer formation. <ref name = "Bachh2007"/> | ||
:The phosphoryl analog <scene name='Sandbox_Reserved_344/P-analog/1'>Beryllofluoride</scene> (BeF<sup>3-</sup>) was used during crystalization of the regulatory domain of ''Escherichia coli''. | :The phosphoryl analog <scene name='Sandbox_Reserved_344/P-analog/1'>Beryllofluoride</scene> (BeF<sup>3-</sup>) was used during crystalization of the regulatory domain of ''Escherichia coli''. | ||
:The Phosphoryl analog made the following bonds: | :The Phosphoryl analog made the following bonds (Fluoride: light green, Magnesium: dark green): | ||
::: BeF<sup>3-</sup> | ::: BeF<sup>3-</sup> | ||
::: F1 to Mg<sup>2+</sup> | ::: F1 to Mg<sup>2+</sup> | ||
::: F2 to Thr 79 | ::: F2 to Thr 79 (Hydrogen Bond) | ||
::: F3 to Lys 101 ( | ::: F3 to Lys 101 (Salt bridge) | ||
=====Un-activated form===== | =====Un-activated form===== | ||
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===Effector domain=== | ===Effector domain=== | ||
When the regulatory domain is phosphorylated, PhoP forms a homodimer. There is no direct change in conformation conferred on the effector domain by the regulatory domain. It is the dimerization that activates the effector domain. The PhoP has a winged helix-turn-helix motif characteristic of the OmpR/PhoB family of response regulators.<ref name = "Hickey"> PMID:19652341</ref> This winged helix-turn-helix allows binding to DNA and regulation of transcription. Binding occurs at tandem repeat promoters with two repeats of the sequence (T/G)GTTTA, known as the PhoP box.<ref name = "Groisman"/> | |||
=Function= | =Function= | ||