C-terminal amides mark proteins for degradation via SCF–FBXO31
A recent “Nature” paper by the groups of Jacob Corn (IMHS, D-BIOL) and Jeffrey Bode (D-CHAB) reveals how cells remove chemically damaged proteins. They discovered that the human SCF–FBXO31 complex scans proteins for C-terminal amidation, a sign of oxidative damaged, and induces their degradation.
Keeping our cells healthy requires a delicate balance of protein production and removal. This process, called protein homeostasis, ensures that damaged or unnecessary proteins are identified and cleared away. How cells distinguish between intact and damaged proteins is poorly understood at the molecular level.
In a recent breakthrough, researchers led by postdocs Matthias Muhar (D-BIOL) and Jakob Farnung (D-CHAB), in collaboration with teams from ETH Zurich, the University of Zurich, and the Max Planck Institute of Biochemistry in Germany, uncovered a new mechanism for removing chemically damaged proteins. They discovered that human proteins can carry chemical modifications, termed C-terminal amides, that remain like a scar after oxidative damage. Most importantly, they found that cells scan their proteins for the presence of this modification and selectively remove such damaged protein fragments. This is achieved by the SCF–FBXO31 complex which can precisely distinguish between intact and amidated C-termini and hands the latter over to the cell’s degradation machinery. This mechanism is likely important for most animal life, as it is highly conserved in distant species, such as sea anemones, and mutations affecting FBXO31 are linked to neurodevelopmental disorders.
This study reveals a new strategy that cells use to surveil their proteins for chemical damage.
Link to the paper in external page Nature.