Journal article
Design principles that protect the proteasome from self-destruction
Protein science, Vol.31(3), pp.556-567
03/2022
DOI: 10.1002/pro.4251
PMCID: PMC8862440
PMID: 34878680
Abstract
The proteasome is a powerful intracellular protease that can degrade effectively any protein, self or foreign, for regulation, quality control, or immune response. Proteins are targeted for degradation by localizing them to the proteasome, typically by ubiquitin tags. At the same time, the proteasome is built from ~33 subunits, and their assembly into the complex and activity are tuned by post-translational modifications on long disordered regions on the subunits. Molecular modeling and biochemical experiments show that some of the disordered regions of proteasomal subunits can access the substrate recognition sites. All disordered regions tested, independent of location, are constructed from amino acid sequences that escape recognition. Replacing a disordered region with a sequence that is recognized by the proteasome leads to self-degradation and, in the case of an essential subunit, cell death.
Details
- Title: Subtitle
- Design principles that protect the proteasome from self-destruction
- Creators
- Amit Kumar Singh Gautam - The University of Texas at AustinHouqing Yu - The University of Texas at AustinChristopher Yellman - The University of Texas at AustinAdrian H Elcock - University of IowaAndreas Matouschek - The University of Texas at Austin
- Resource Type
- Journal article
- Publication Details
- Protein science, Vol.31(3), pp.556-567
- DOI
- 10.1002/pro.4251
- PMID
- 34878680
- PMCID
- PMC8862440
- NLM abbreviation
- Protein Sci
- ISSN
- 0961-8368
- eISSN
- 1469-896X
- Grant note
- R01 GM135264 / NIGMS NIH HHS U54 GM105816 / NIGMS NIH HHS R21 CA196456 / NCI NIH HHS R35 GM122466 / NIGMS NIH HHS R01 GM124501 / NIGMS NIH HHS
- Language
- English
- Date published
- 03/2022
- Academic Unit
- Physics and Astronomy; Biochemistry and Molecular Biology
- Record Identifier
- 9984293087402771
Metrics
21 Record Views