Sigma factors may be inhibited by proteins known as anti-sigma factors. These bind to specific alternative sigma factors and prevent them from associating with RNA polymerase (Fig. 9.08). When oF is first made in the developing spore, it is inactive. Unlike oE and oK, which need to be activated by the proteolysis of an inactive precursor protein, oF is kept inactive by an anti-sigma factor (SpoIIAB). This anti-sigma factor is, in turn, displaced from oF by an anti-anti-sigma factor (SpoIIAA). This event triggers the cascade of gene activation described above.
Regulation of alternative sigma factors by binding to anti-sigma factors and their release by anti-anti-sigma factors is not especially common, but several examples are known. Assembly of flagella in E. coli and Salmonella is under control of the FliA sigma factor and the FlgM anti-sigma factor. A clinically important example is the production of mucus by Pseudomonas aeruginosa. This bacterium often infects the lungs of cystic fibrosis patients, where it switches on the genes for mucus production. These are under control of the alternative sigma factor AlgU and the anti-sigma factor MucA. The bacterial mucus clogs the patient's airways and is a major contributor to the symptoms of the disease. Strictly speaking, the material made by Pseudomonas is alginate, an acidic polysaccharide that is a repeating polymer of mannuronic and glucuronic acids. This is chemically distinct from the true mucus made by animal cells, which con-
anti-anti-sigma factor Protein that binds to an anti-sigma factor and so prevents the anti-sigma factor from binding to and inhibiting a sigma factor anti-sigma factor Protein that binds to a sigma factor and blocks its role in the initiation of transcription
Activators and Repressors Participate in Positive and Negative Regulation 243
8s together in spore
The anti-sigma factor SpoIIAB binds to sF and inactivates it. When the cell receives an external signal, the phosphorylated form of SpoIAA, an anti-anti-sigma factor, loses its phosphate and engages SpoIIAB. This releases sF, which is then free to activate the sporulation cascade shown above in Fig 9.07.
eg s F is inactive when bound to Spoil AB
s F is released s F is released o
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