Modulation of the bacterial CobB sirtuin deacylase activity by N-terminal acetylation.

Abstract

In eukaryotic cells, the N-terminal amino moiety of many proteins is modified by N-acetyltransferases (NATs). This protein modification can alter the folding of the target protein; can affect binding interactions of the target protein with substrates, allosteric effectors, or other proteins; or can trigger protein degradation. In prokaryotes, only ribosomal proteins are known to be N-terminally acetylated, and the acetyltransferases responsible for this modification belong to the Rim family of proteins. Here, we report that, in <i>Salmonella enterica</i>, the sirtuin deacylase CobB long isoform (CobB_L) is N-terminally acetylated by the YiaC protein of this bacterium. Results of in vitro acetylation assays showed that CobB_L was acetylated by YiaC; liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to confirm these results. Results of in vitro and in vivo experiments showed that CobB_L deacetylase activity was negatively affected when YiaC acetylated its N terminus. We report 1) modulation of a bacterial sirtuin deacylase activity by acetylation, 2) that the Gcn5-related YiaC protein is the acetyltransferase that modifies CobB_L, and 3) that YiaC is an NAT. Based on our data, we propose the name of NatA (<i>N</i>-acyltransferase A) in lieu of YiaC to reflect the function of the enzyme.