The membrane-bound transcriptional regulator CadC is activated by proteolytic cleavage in response to acid stress.
Proteolytic processes often participate in signal transduction across bacterial membranes. In Salmonella enterica serovar Typhimurium, the transcriptional regulator CadC activates genes of lysine decarboxylase system in response to external acidification and exogenous lysine. However, the signaling mechanism of CadC activation remains unexplored. We report here that CadC is located on the inner membrane under normal growth conditions but rapidly cleaved under acid stress conditions, leading to the induction of target gene transcription. As full-length CadC is degraded, the N-terminal fragment containing the DNA-binding domain accumulates in the inner membrane. Moreover, we show that C-terminal truncations of CadC abolish its degradation, resulting in complete loss of activator function. Together, these observations suggest that site-specific proteolysis at the periplasmic domain of CadC generates a biologically active form of N-terminal DNA-binding domain to promote target gene activation.
Lee
Yong Heon
YH
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
Kim
Ji Hye
JH
Bang
Iel Soo
IS
Park
Yong Keun
YK
D000143:Acids / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*
D000143:Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C080050:CadC protein, Bacteria