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A nucleotide‐dependent switch in proteasome assembly mediated by the Nas6 chaperone
Author(s) -
Park Soyeon,
Li Frances,
Sokolova Vladyslava
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.526.41
Subject(s) - proteasome , protein subunit , atp hydrolysis , nucleotide , chaperone (clinical) , atpase , biochemistry , chemistry , ubiquitin , hydrolysis , microbiology and biotechnology , biophysics , biology , enzyme , medicine , pathology , gene
The proteasome is a molecular machine essential for protein degradation. The proteasome is assembled via the 9‐subunit lid, 9‐subunit base, and 28‐subunit core particle (CP). Previous work has shown that the chaperones Rpn14, Nas6, Hsm3, and Nas2 each bind a specific ATPase subunit of the base, and antagonize base‐CP interaction. Here we show that the Nas6 chaperone also obstructs base‐lid association. Nas6 alternates between these two inhibitory modes according to the nucleotide state of the base. When ATP cannot be hydrolyzed, Nas6 interferes with base‐lid, but not base‐CP association. In contrast, under conditions of ATP hydrolysis, Nas6 obstructs base‐CP, but not base‐lid association. Modeling of Nas6 into cryo‐EM structures of the proteasome suggests that Nas6 controls both base‐lid affinity and base‐CP affinity through steric hindrance; Nas6 clashes with the lid in the ATP‐hydrolysis‐blocked proteasome, but clashes instead with the CP in the ATP‐hydrolysis‐competent proteasome. Thus, Nas6 provides a dual mechanism to control assembly at both major interfaces of the proteasome. Support or Funding Information Boettcher Webb‐Waring Biomedical Research Award This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .