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{{STRUCTURE_2pl1|PDB=2pl1|SCENE=}}

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=Introduction=
PhoP is a cytoplasmic response regulator from the two component system PhoP/PhoQ. This system responds mainly to changes in extracellular Mg2+ concentration and is an important trigger for gram-negative bacteria such as Escherichia coli and Salmonella enterica to become virulent. PhoQ, located across the inner membrane, responds to low Mg2+ concentration by phosphorylating PhoP. Gene regulation and other two component systems respond to the phosphorylated PhoP. Gene regulation is achieved by increased affinity of the homodimer to the PhoP box, a tandem repeat promoter. The response is organism specific but generally involves survival in low Mg2+ environments and virulence.

=Structure=
PhoP consists of 2 domains, the regulatory domain and the C-terminal effector domain.

===Regulatory Domain===
The regulatory domain consists of 5 α helixes and 5 β sheets. Twofold symmetry is achieved on the α-4 helix – β-5 sheet – α-5 helix face. The regulatory domain may be phosphorylated at a conserved aspartate by PhoQ, a histidine protein kinase. Phosphorylation of this aspartate stabilizes the homodimer.
The PhoP regulatory domain has intrinsic autophosphatase activity, allowing it to inactivate itself after a delay.

=====Unactivated form=====
Under normal physiological conditions, unactivated PhoP occurs mainly as a monomer. At higher concentration unactivated PhoP has been shown to dimerize and act in a similar way to activated and dimerized PhoP. Many regulatory domains isolated from members of the OmpR/PhoB family and in their inactive form, crystalize in a form similar to their activated dimers.

=====Activated form=====
Phosphorylation of the regulatory domain stabilizes dimer formation.
BeF3-: Phosphoryl analog
F1 to Mg2+
F2 to Thr 79 (Correlated with Ala 80) -> F3?
& BBone of Gly 53
F3 to Lys 101 (salt bridge)

===Effector domain===
The effector domain is activated when PhoP is in dimer form. There is no direct change in conformation conferred on the effector domain by the regulatory domain. The PhoP has a winged helix-turn-helix motif characteristic of the OmpR/PhoB family of response regulators. This winged helix-turn-helix allows binding to DNA and regulation of transcription. Binding occurs at promoters with two repeats of the sequence (T/G)GTTTA, known as the PhoP box.

=Function=
Two component systems allow bacteria to respond to changes in their environment. These systems are found mainly in prokaryotes and a few eukaryotes (mack). The PhoP/PhoQ system, found specifically in gram-negative bacteria, react mainly to a drop in extracellular Mg2+. Since the magnesium concentration is typically lower inside the host cell compared to outside, this acts as a trigger to become virulent. Other functions activated by the PhoP/PhoQ system includes adaptation to low Mg2+ conditions, changes in cell wall, expression of proteases to protect against antimicrobial peptides and various other species specific responses. PhoP in Salmonella enterica regulates up to 40 proteins. (Groisman)
PhoP is not limited to direct regulation of gene expression. PhoP may regulate other two component systems at transcription, posttranscription and posttranslation too, in fact PhoP activates the expression of its own phoP gene, resulting in positive feedback and definite conversion to virulence.
The PhoP/PhoQ system may olso be found in non-cytoplasmic pathogens, such as rwinia carotovora supsb. carotovora, a plant pathogen living in the intercellular fluid, or non-pathogenic bacteria (????)

=Importance of PhoP=
The Function of PhoP/PhoQ to successfully become virulent, makes it a promising target for vaccine and antimicrobial drug development.

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[[Sandbox_Reserved_344#Sec1.1| Jump to Sec1.1]]
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This is referenced from randomly selected article<ref name = "placehoder"> PMID:17884906 </ref>

 

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