The ZZ domain of HERC2 is a receptor of arginylated substrates

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 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 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.

• Publication year

  2022

• Venue

  Scientific Reports

• Publication date

  2022-04-11

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41598-022-10119-wPMID 35411094PMCID 9001736
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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