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{{STRUCTURE_2pl1|PDB=2pl1|SCENE=}} | {{STRUCTURE_2pl1|PDB=2pl1|SCENE=}} | ||
__TOC__ | __TOC__ | ||
=Introduction= | =Introduction= | ||
PhoP is a cytoplasmic response regulator from the two component system PhoP/PhoQ. This system responds mainly to changes in extracellular Mg<sup>2+</sup> concentration and is an important part of the signal pathway leading to a coordinated cell response in gram-negative bacteria such as ''Escherichia coli'' and ''Salmonella enterica''. PhoQ, located across the inner membrane, responds to low Mg<sup>2+</sup> concentration by phosphorylating PhoP. Phosphorylated PhoP forms a homodimer and affects gene expression and other two component systems. 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 survival in low Mg2+ environments and virulence. <ref name = "Bachh2007"> PMID:17545283</ref><ref name = "Groisman"> PMID:11222580</ref> | PhoP is a cytoplasmic response regulator from the two component system PhoP/PhoQ. This system responds mainly to changes in extracellular Mg<sup>2+</sup> concentration and is an important part of the signal pathway leading to a coordinated cell response in gram-negative bacteria such as ''Escherichia coli'' and ''Salmonella enterica''. PhoQ, located across the inner membrane, responds to low Mg<sup>2+</sup> concentration by phosphorylating PhoP. Phosphorylated PhoP forms a homodimer and affects gene expression and other two component systems. 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 survival in low Mg2+ environments and virulence. <ref name = "Bachh2007"> PMID:17545283</ref><ref name = "Groisman"> PMID:11222580</ref> | ||
=Structure= | =Structure= | ||
PhoP consists of 2 domains, the regulatory domain and the C-terminal effector domain.<ref name = "Bachh2007"/> | PhoP consists of 2 domains, the regulatory domain and the C-terminal effector domain.<ref name = "Bachh2007"/> | ||
===Regulatory 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 and 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.<ref name = "Bachh2007"/> | The regulatory domain consists of 5 α-helixes and 5 β-sheets. Twofold symmetry is achieved on the α-4 helix, β-5 sheet and 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.<ref name = "Bachh2007"/> | ||
The PhoP regulatory domain has intrinsic autophosphatase activity, allowing it to inactivate itself after a delay. | The PhoP regulatory domain has intrinsic autophosphatase activity, allowing it to inactivate itself after a delay.<ref name = "Perron-S"> PMID:17125150</ref> | ||
=====Un-activated form===== | =====Un-activated form===== | ||
:Under normal physiological conditions, unactivated PhoP occurs mainly as a monomer. At higher concentration unactivated PhoP has been shown to dimerize and act similar 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. | :Under normal physiological conditions, unactivated PhoP occurs mainly as a monomer. At higher concentration unactivated PhoP has been shown to dimerize and act similar 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. | ||
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: & BBone of Gly 53 | : & BBone of Gly 53 | ||
:F3 to Lys 101 (salt bridge) | :F3 to Lys 101 (salt bridge) | ||
===Effector domain=== | ===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.<ref name = "Hickey"> PMID:19652341</ref> 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.<ref name = "Groisman"/> | 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.<ref name = "Hickey"> PMID:19652341</ref> 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.<ref name = "Groisman"/> | ||
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The PhoP/PhoQ system may also be found in non-cytoplasmic pathogens, such as ''Erwinia carotovora supsb. carotovora'', a plant pathogen living in the intercellular fluid, or non-pathogenic bacteria. <ref name = "Groisman"/> | The PhoP/PhoQ system may also be found in non-cytoplasmic pathogens, such as ''Erwinia carotovora supsb. carotovora'', a plant pathogen living in the intercellular fluid, or non-pathogenic bacteria. <ref name = "Groisman"/> | ||
=Importance of PhoP= | =Importance of PhoP= | ||
PhoP/PhoQ plays in key role in certain bacteria becoming virulent. For example, ''Salmonella typhimurium'' becomes avirulent when it carries a phoP mutation.<ref name = "Groisman1989"> PMID:2674945</ref> This makes it a promising target for vaccine and antimicrobial drug development. | PhoP/PhoQ plays in key role in certain bacteria becoming virulent. For example, ''Salmonella typhimurium'' becomes avirulent when it carries a phoP mutation.<ref name = "Groisman1989"> PMID:2674945</ref> This makes it a promising target for vaccine and antimicrobial drug development. | ||
=References= | =References= | ||
<references/> | <references/> | ||