Ubp6 deubiquitinase controls conformational dynamics and substrate degradation of the 26S proteasome

Details

• Alternative Title:
  Nat Struct Mol Biol
• Personal Author:
  Bashore, Charlene ; Dambacher, Corey M. ; Goodall, Ellen A. ; Matyskiela, Mary E. ; Lander, Gabriel C. ; Martin, Andreas
• Description:
  Substrates are targeted for proteasomal degradation through the attachment of ubiquitin chains that need to be removed by proteasomal deubiquitinases before substrate processing. In budding yeast, the deubiquitinase Ubp6 trims ubiquitin chains and affects substrate processing by the proteasome, but the underlying mechanisms and the location of Ubp6 within the holoenzyme have been elusive. Here we show that Ubp6 activity strongly responds to interactions with the base ATPase and the conformational state of the proteasome. Electron microscopy analyses reveal that ubiquitin-bound Ubp6 contacts the N ring and AAA+ ring of the ATPase hexamer and is in proximity to the deubiquitinase Rpn11. Ubiquitin-bound Ubp6 inhibits substrate deubiquitination by Rpn11, stabilizes the substrate-engaged conformation of the proteasome and allosterically interferes with the engagement of a subsequent substrate. Ubp6 may thus act as a ubiquitin-dependent 'timer' to coordinate individual processing steps at the proteasome and modulate substrate degradation.
• Subjects:
  Endopeptidases Macromolecular Substances Microscopy, Electron Multienzyme Complexes Proteasome Endopeptidase Complex Saccharomyces Cerevisiae Saccharomyces Cerevisiae Proteins
• Source:
  Nat Struct Mol Biol. 22(9):712-719.
• Pubmed ID:
  26301997
• Pubmed Central ID:
  PMC4560640
• Document Type:
  Journal Article
• Funding:
  DP2 EB020402/EB/NIBIB NIH HHS/United States ; DP2 EB020402-01/DP/NCCDPHP CDC HHS/United States ; R01 GM094497/GM/NIGMS NIH HHS/United States ; R01-GM094497/GM/NIGMS NIH HHS/United States ; T32 GM066698/GM/NIGMS NIH HHS/United States
• Volume:
  22
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d367f1b08a710b04af0ba67d82ba3949eddf4cc1b73953a33b1daf60827f6ae4
• Download URL:
  https://stacks.cdc.gov/view/cdc/36271/cdc_36271_DS1.pdf
• File Type:
  [PDF - 1.64 MB ]