FtsH degrades kinetically stable dimers of cyclopropane fatty acid synthase via an internal degron. Issue 1 (14th December 2022)

• Record Type: Journal Article
• Authors: Hari, Sanjay B.; Morehouse, Juhee P.; Baker, Tania A.; Sauer, Robert T.
• Is Part Of: Molecular microbiology. Volume 119:Issue 1(2023)
• Page Start: 101
• Page End: 111
• Publication Date: 2022-12-14
• Subjects: AAA+ protease -- ATP‐dependent protein degradation -- substrate recognition; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.15009
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: Targeted protein degradation plays important roles in stress responses in all cells. In E. coli, the membrane‐bound AAA+ FtsH protease degrades cytoplasmic and membrane proteins. Here, we demonstrate that FtsH degrades cyclopropane fatty acid (CFA) synthase, whose synthesis is induced upon nutrient deprivation and entry into stationary phase. We find that neither the disordered N‐terminal residues nor the structured C‐terminal residues of the kinetically stable CFA‐synthase dimer are required for FtsH recognition and degradation. Experiments with fusion proteins support a model in which an internal degron mediates FtsH recognition as a prelude to unfolding and proteolysis. These findings elucidate the terminal step in the life cycle of CFA synthase and provide new insight into FtsH function. Abstract : The cellular proteome is in a constant state of flux, as changes in the environment necessitate rapid functional responses, often via mechanisms involving protein degradation. FtsH, a membrane‐bound AAA+ protease, degrades cyclopropane fatty acid synthase, an enzyme that is transiently upregulated upon entrance into stationary phase. Interestingly, FtsH appears to utilize an internal sequence of CFA synthase for substrate recognition rather than degrons at either the N‐ or C‐terminus.