HflK

HflK is a periplasmic-inner-membrane protein found in many Gram-negative bacteria, most notably Escherichia coli. It functions as part of a regulatory complex with HflC to modulate the activity of the essential ATP-dependent protease FtsH (also known as HflB). Together, HflK and HflC form a membrane-associated complex that influences which substrates are degraded by FtsH and how efficiently degradation occurs.

Structure and localization: HflK is anchored in the inner membrane by an N-terminal transmembrane segment and features a large periplasmic domain. It forms a complex with HflC and interacts with FtsH to regulate proteolysis. The precise architecture and stoichiometry of the HflK/HflC/FtsH complex have been subjects of structural and biochemical study, with the periplasmic regions mediating regulatory contacts.

Function and significance: The HflK/HflC complex modulates FtsH protease activity and substrate specificity, thereby influencing membrane protein quality control and envelope stress responses. While FtsH is essential for viability in many bacteria, the regulatory impact of HflK and HflC can affect growth under stress and the turnover of certain regulatory proteins and membrane proteins. The exact mechanism by which HflK/HflC alters FtsH activity remains an area of active research, with models proposing allosteric regulation or substrate access control.

Genetics and distribution: The hflK gene encodes HflK, and the hflC gene encodes HflC. In many species these genes are located adjacent to each other and are studied as a regulatory pair controlling FtsH-mediated proteolysis.

See also: FtsH protease; HflC.