HflBFtsH

HflBFtsH refers to the protease FtsH, encoded by the hflB gene in many bacteria, including Escherichia coli. The naming reflects its historical designation as HflB and its product FtsH, a membrane-bound ATP-dependent metalloprotease. FtsH forms a hexameric complex anchored in the inner membrane by its N-terminal transmembrane segments, with the cytoplasmic AAA+ ATPase and protease domains driving proteolysis. Its activity is modulated by regulatory proteins HflK and HflC, which associate with FtsH and influence substrate selection and proteolytic rate in response to cellular conditions.

FtsH is an essential, ATP-dependent protease that degrades misfolded membrane proteins and certain regulatory proteins. Among its substrates is the heat-shock transcription factor sigma32 (RpoH); by regulating the levels of RpoH, FtsH helps tune the bacterial heat-shock response and maintain protein quality control. Proteolysis occurs through the central translocation channel of the hexamer, powered by ATP hydrolysis, with a Zn2+-dependent catalytic site in the protease domain.

FtsH is widely conserved among bacteria and is often essential for viability, making it a central component of protein quality control and regulator turnover. The HflKC-FtsH regulatory axis serves as a model for understanding how cells balance degradation and stability of membrane and cytosolic substrates. In addition to basic biology, FtsH and its regulators have been explored as potential targets for antimicrobial strategies.

Related topics include FtsH, HflK, HflC, and RpoH (sigma32).