An unstructured initiation site is required for efficient proteasome-mediated degradation

Sumit Prakash, Lin Tian, Kevin S. Ratliff, Rebecca E. Lehotzky, Andreas Matouschek

Research output: Contribution to journalArticle

295 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)830-837
Number of pages8
JournalNature Structural and Molecular Biology
Volume11
Issue number9
DOIs
StatePublished - Sep 2004
Externally publishedYes

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Proteasome Endopeptidase Complex
Ubiquitin
Proteolysis
Proteins
ATP-Dependent Proteases
Polyubiquitin
Eukaryotic Cells
Cytosol

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

An unstructured initiation site is required for efficient proteasome-mediated degradation. / Prakash, Sumit; Tian, Lin; Ratliff, Kevin S.; Lehotzky, Rebecca E.; Matouschek, Andreas.

In: Nature Structural and Molecular Biology, Vol. 11, No. 9, 09.2004, p. 830-837.

Research output: Contribution to journalArticle

Prakash, Sumit ; Tian, Lin ; Ratliff, Kevin S. ; Lehotzky, Rebecca E. ; Matouschek, Andreas. / An unstructured initiation site is required for efficient proteasome-mediated degradation. In: Nature Structural and Molecular Biology. 2004 ; Vol. 11, No. 9. pp. 830-837.
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