The Markey Scholars Conference Proceedings (2004) / Chapter Skim
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9 Signal Transduction in Bacteria
9 Signal Transduction in Bacteria
Pages 80-89
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From page 80... ...
Rather, in this particular case, phosphorylation serves to provide phosphoryl groups for transfer to the second component, a protein called the response regulator. In bacteria, these systems largely replace the small GTPase signaling pathways (such as those involving members of the ras super family)
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From page 81... ...
In a typical system, consisting of just two components, the histidine kinase is a transmembrane protein with a variable extracellular sensing domain and a conserved intracellular kinase domain. Phosphoryl transfer occurs to the conserved domain of the response regulator that in turn, controls the activity of an associated variable effector domain.
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From page 82... ...
It is this conserved response regulator domain that is actually responsible for the catalysis of phosphoryl transfer from the histidine kinase, specifically to an aspartic acid residue that is located at the C-terminal end of the third and central beta strand. There is also another set of conserved residues that are located on adjacent beta strands 3445, creating a diagonal path leading away from the active site.
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From page 83... ...
There are dozens of structures of isolated regulatory domains and about a half dozen structures of isolated effector domains in the Protein Data Bank. But the structures of intact multidomain-response regulators have been relatively resistant to structural analysis.
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From page 84... ...
In the chemotaxis system there are actually two-response regulators that obtain phosphoryl groups from the single histidine kinase. The chemoreceptors, through a coupling protein, control the activity of the histidine kinase CheA, which passes phosphoryl groups to CheY, which acts at the flagellar motor to induce the physiological response.
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From page 85... ...
A space-filling model of structure of the intact methylesterase illustrates a very tight packing of the regulatory domain against the catalytic domain, almost completely blocking access to the catalytic triad of the active site. In a modeling experiment, we attempted to dock the methylation region of the receptor, specifically a helix with glutamate residues, near the active site serine nucleophile of the catalytic domain.
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From page 86... ...
coli genome conducted by Mizuno several years ago, revealed that out of the 32 response regulators in E coli, 25 of them could be categorized as belonging to the previously identified three subfamilies of transcription factors based on homology within their DNAbinding domains.
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From page 87... ...
EnvZ provides phosphoryl groups to the response regulator OmpR, which functions as a transcription factor. The C-terminal, or effector, domain of this response regulator is a DNA-binding domain, and OmpR, in its phosphorylated state, binds in a hierarchical fashion to binding sites that are located upstream of the genes that encode the major outer membrane porin proteins, OmpF and OmpC.
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From page 88... ...
The two response regulators for which structures have been known for several years have served as a model for understanding interdomain regulation. In both cases, there are large domain interfaces and the regulatory domains pack against the C-terminal effector domains, essentially precluding access to the functional regions of the effector domains: the active site of the methylesterase CheB, and the recognition helix of the transcription factor NarL.
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From page 89... ...
Rather than a mechanism of regulation involving intra-molecular communication between the regulatory and effector domains within a monomer, the regulation within DrrD, and perhaps other members of the OmpR/PhoB subfamily, appears to occur through inter-molecular interactions. Specifically, activation is proposed to proceed primarily through dimerization of the phosphorylated regulatory domains with the effector domains participating as passive partners.
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