Bacterial sensing: A putative amphipathic helix in RsiV is the switch for activating σV in response to lysozyme
| Autor: | Ute Müh, Paige J. Kies, Craig D. Ellermeier, Lincoln T. Lewerke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Bacillus Bacillus subtilis Pathology and Laboratory Medicine Biochemistry Mechanical Treatment of Specimens chemistry.chemical_compound Cell Signaling Medicine and Health Sciences Membrane Receptor Signaling Amino Acids Post-Translational Modification Cell Disruption Genetics (clinical) Signal peptidase Organic Compounds Helix-Loop-Helix Motifs Serine Endopeptidases Proteases Signaling Cascades Enzymes Bacterial Pathogens Chemistry Bacillus Subtilis Experimental Organism Systems Specimen Disruption Medical Microbiology Physical Sciences Prokaryotic Models Lysozyme Basic Amino Acids Pathogens Hydrophobic and Hydrophilic Interactions Signal Peptides Protein Binding Research Article Signal Transduction Signal peptide lcsh:QH426-470 030106 microbiology Sigma Factor Biology Cleavage (embryo) Research and Analysis Methods Regulated Intramembrane Proteolysis Microbiology Stress Signaling Cascade 03 medical and health sciences Bacterial Proteins Protein Domains Genetics Sulfur Containing Amino Acids Cysteine Molecular Biology Microbial Pathogens Ecology Evolution Behavior and Systematics Bacteria Lysine Cell Membrane Organic Chemistry Chemical Compounds Organisms Membrane Proteins Biology and Life Sciences Proteins Cell Biology biology.organism_classification lcsh:Genetics chemistry Cytoplasm Specimen Preparation and Treatment Proteolysis Biophysics Enzymology Muramidase |
| Zdroj: | PLoS Genetics, Vol 14, Iss 7, p e1007527 (2018) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Extra Cytoplasmic Function (ECF) σ factors are a diverse group of alternate σ factors bacteria use to respond to changes in the environment. The Bacillus subtilis ECF σ factor σV responds to lysozyme. In the absence of lysozyme, σV is held inactive by the anti-σ factor, RsiV. In the presence of lysozyme RsiV is degraded via regulated intramembrane proteolysis, which results in the release of σV and thus activation of lysozyme resistance genes. Signal peptidase is required to initiate degradation of RsiV. Previous work indicated that RsiV only becomes sensitive to signal peptidase upon direct binding to lysozyme. We have identified a unique domain of RsiV that is responsible for protecting RsiV from cleavage by signal peptidase in the absence of lysozyme. We provide evidence that this domain contains putative amphipathic helices. Disruption of the hydrophobic surface of these helices by introducing positively charged residues results in constitutive cleavage of RsiV by signal peptidase and thus constitutive σV activation. We provide further evidence that this domain contains amphipathic helices using a membrane-impermeable reagent. Finally, we show that upon lysozyme binding to RsiV, the hydrophobic face of the amphipathic helix becomes accessible to a membrane-impermeable reagent. Thus, we propose the amphipathic helices protect RsiV from cleavage in the absence of lysozyme. Additionally, we propose the amphipathic helices rearrange to form a suitable signal peptidase substrate upon binding of RsiV to lysozyme leading to the activation of σV. Author summary Signal transduction involves (i) sensing a signal, (ii) a molecular switch triggering a response, and (iii) altering gene expression. For Bacillus subtilis’ response to lysozyme, we have a detailed understanding of (i) and (iii). Here we provide insights for a molecular switch that triggers the lysozyme response via σV activation. RsiV, an inhibitor of σV activity, is cleaved by signal peptidase only in the presence of lysozyme. Signal peptidase constitutively cleaves substrates that are translocated across the membrane. A domain-of-unknown-function (DUF4179) in RsiV contains the signal peptidase cleavage site, and protects RsiV from cleavage in the absence of lysozyme via amphipathic helices. In addition to RsiV, DUF4179 is found in an unrelated and uncharacterized anti-σ factor present in Firmicutes including within some clinically-relevant species. |
| Databáze: | OpenAIRE |
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