The ZZ domain of HERC2 is a receptor of arginylated substrates

The ZZ domain of HERC2 is a receptor of arginylated substrates

Blog Article

Abstract The E3 ubiquitin ligase HERC2 has been linked to neurological diseases and cancer, however it remains a poorly characterized human protein.Here, we show that the ZZ domain of HERC2 (HERC2ZZ) recognizes a mimetic of the Nt-R cargo Hair Rinse degradation signal.NMR titration experiments and mutagenesis results reveal that the Nt-R mimetic peptide occupies a well-defined binding site of HERC2ZZ comprising of the Course a pied - Accessoires - Hydratation - Ceinture negatively charged aspartic acids.

We report the crystal structure of the DOC domain of HERC2 (HERC2DOC) that is adjacent to HERC2ZZ and show that a conformational rearrangement in the protein may occur when the two domains are linked.Immunofluorescence microscopy data suggest that the stimulation of autophagy promotes targeting of HERC2 to the proteasome.Our findings suggest a role of cytosolic HERC2 in the ubiquitin-dependent degradation pathways.