RfaA (YqhY), a novel adaptor protein, controls metabolite-sensitive protein degradation in Bacillus subtilis

The carboxylation of acetyl-CoA is the committed step of fatty acid synthesis catalyzed by the multisubunit acetyl-CoA carboxylase (ACCase). However, the mechanisms that control the activity of this enzyme are poorly understood. Here, we identify the so far unknown protein RfaA (YqhY) of the model bacterium Bacillus subtilis as a regulator of fatty acid acquisition that targets the AccC subunit of ACCase for degradation. RfaA interacts with both AccC and the ClpE unfoldase subunit of the ClpEP protease complex. While the former interaction is not sensitive to the physiological conditions, RfaA interacts with ClpE only in the absence of the global amino group donor glutamate. This results in the degradation of AccC in the absence of glutamate. The inactivation of the rfaA gene results in the accumulation of fatty acids in the cell and in the formation of lipid droplets which are toxic for the bacteria. The reduced fatty acid synthesis in the absence of glutamate as a result of RfaA-and ClpEP-dependent degradation of AccC thus prevents intoxication of the cells by fatty acids. Our findings suggest that the degradation of enzymes that catalyze the committed step of biosynthetic pathways might be an important mechanism to control cellular homeostasis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/580884v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1f09555org.highwire.dtl.DTLVardef@1dc12e8org.highwire.dtl.DTLVardef@15d6961org.highwire.dtl.DTLVardef@1b1923e_HPS_FORMAT_FIGEXP M_FIG C_FIG