We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
An unstructured initiation site is required for efficient proteasome-mediated degradation.
- Authors
Prakash, Sumit; Tian, Lin; Ratliff, Kevin S; Lehotzky, Rebecca E; Matouschek, Andreas
- Abstract
The proteasome is the main ATP-dependent protease in eukaryotic cells and controls the concentration of many regulatory proteins in the cytosol and nucleus. Proteins are targeted to the proteasome by the covalent attachment of polyubiquitin chains. The ubiquitin modification serves as the proteasome recognition element but by itself is not sufficient for efficient degradation of folded proteins. We report that proteolysis of tightly folded proteins is accelerated greatly when an unstructured region is attached to the substrate. The unstructured region serves as the initiation site for degradation and is hydrolyzed first, after which the rest of the protein is digested sequentially. These results identify the initiation site as a novel component of the targeting signal, which is required to engage the proteasome unfolding machinery efficiently. The proteasome degrades a substrate by first binding to its ubiquitin modification and then initiating unfolding at an unstructured region.
- Publication
Nature structural & molecular biology, 2004, Vol 11, Issue 9, p830
- ISSN
1545-9993
- Publication type
Journal Article
- DOI
10.1038/nsmb814