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

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.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Prakash S,Tian L,Ratliff KS,Lehotzky RE,Matouschek A

doi

10.1038/nsmb814

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

830-7

issue

9

eissn

1545-9993

issn

1545-9985

pii

nsmb814

journal_volume

11

pub_type

杂志文章

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