Scientists decode the mechanics of a bacterial protein essential to all E. coli
Researchers have mapped how FtsH, a crucial bacterial enzyme, consumes energy and breaks down other proteins—work that could unlock new antibiotic targets. Understanding this protease's molecular choreography offers a foundation for developing drugs that disable bacteria without harming human cells, a key challenge in fighting resistant infections.
Originaltitel: Functional details of the integral membrane metallo-protease FtsH revealed by solution NMR spectroscopy
Abstract The bacterial FtsH protease resides in the inner leaflet of the bacterial inner membrane and is the sole essential protease found in Escherichia Coli ( E. coli ). FtsH’s mandatory role is due to its proteolytic regulation of a key enzyme in the lipopolysaccharide (LPS) assembly, LpxC, although FtsH substrates comprise a diverse pool of both soluble and membrane proteins. While the full-length structure of FtsH could be solved recently, large parts of its functional cycle remain poorly understood. Here, we use advanced solution NMR spectroscopy methods in combination with biochemical assays to elucidate its ATPase cycle at an unprecedented level of detail. We reveal the foundation of the interdomain communication based on subtly tuned protein dynamics mediated via key NOE contacts as well as the kinetic rates underlying ATP consumption, providing a detailed level of insight into the interplay between the individual FtsH sub-domains, that drive the proteolytic cycle.