Which enzyme trims mannose residues to signal degradation of misfolded proteins?
Distinguishing proteins still capable of folding from terminally misfolded clients destined for destruction relies on slow enzymatic removal of mannose residues acting as molecular clock. ER mannosidase I and ER-degradation-enhancing α-mannosidase-like proteins EDEM1, EDEM2 and EDEM3, which are catalytically active despite name suggesting lectin, cleave specific α1-2 linked mannoses from outer branches of high-mannose N-glycan. Initial Man9 processed to Man8B isoform, then after prolonged ER residence to Man7, Man6 species lacking terminal mannose on C-branch, disfavoring interaction with regl
Ref: Mast & Ng, Crit Rev Biochem Mol Biol 47: 2012, Mannose Trimming Signals ERAD.