Allosteric control of Ubp6 and the proteasome via a bidirectional switch
2022 | journal article; research paper. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
Allosteric control of Ubp6 and the proteasome via a bidirectional switch
Hung, K. Y. S.; Klumpe, S.; Eisele, M. R.; Elsasser, S.; Tian, G.; Sun, S. & Moroco, J. A. et al. (2022)
Nature Communications, 13(1) art. 838. DOI: https://doi.org/10.1038/s41467-022-28186-y
Documents & Media
s41467-022-28186-y.pdf2.33 MBAdobe PDF41467_2022_28186_MOESM1_ESM.pdf15.72 MBAdobe PDF41467_2022_28186_MOESM2_ESM.docx41.54 kBMicrosoft Word XML41467_2022_28186_MOESM3_ESM.xlsx643.21 kBMicrosoft Excel XML41467_2022_28186_MOESM4_ESM.pdf1.24 MBAdobe PDF41467_2022_28186_MOESM5_ESM.zip12.05 MBUnknown
Details
- Authors
- Hung, Ka Ying Sharon; Klumpe, Sven; Eisele, Markus R.; Elsasser, Suzanne; Tian, Geng; Sun, Shuangwu; Moroco, Jamie A.; Cheng, Tat Cheung ; Joshi, Tapan; Seibel, Timo; Finley, Daniel
- Abstract
- Abstract The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome through deubiquitination and a noncatalytic effect. Here, we report cryo-EM structures of the proteasome bound to Ubp6, based on which we identify mutants in Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations define a conserved region that we term the ILR element. The ILR is found within the BL1 loop, which obstructs the catalytic groove in free Ubp6. Rpt1-ILR interaction opens the groove by rearranging not only BL1 but also a previously undescribed network of three interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition are linked in that they are eliminated by the same mutations. Ubp6 and ubiquitin together drive proteasomes into a unique conformation associated with proteasome inhibition. Thus, a multicomponent allosteric switch exerts simultaneous control over both Ubp6 and the proteasome.
- Issue Date
- 2022
- Journal
- Nature Communications
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Sakata (Structural Biology of Protein Quality Control)
- eISSN
- 2041-1723
- Language
- English