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PMID: 21278740 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Defining the geometry of the two-component proteasome degron.

Nature chemical biology ·Vol. 7 ·No. 3 ·2011-03-00 ·Pages 161-7

Inobe T, Fishbain S, Prakash S, Matouschek A

Abstract

The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the initiation region for proteasomal proteolysis. Here we have characterized how the arrangement of the two degron parts in a protein affects degradation. We found that a substrate is degraded efficiently only when its initiation region is of a certain minimal length and is appropriately separated in space from the proteasome-binding tag. Regions that are located too close or too far from the proteasome-binding tag cannot access the proteasome and induce degradation. These spacing requirements are different for a polyubiquitin chain and a ubiquitin-like domain. Thus, the arrangement and location of the proteasome initiation region affect a protein's fate and are important in selecting proteins for proteasome-mediated degradation.

MeSH Terms
Binding Sites Catalysis Escherichia coli/metabolism Escherichia coli Proteins/chemistry,metabolism Humans Immunoglobulins/chemistry,metabolism Neurospora crassa/metabolism Polyubiquitin/chemistry,metabolism Proteasome Endopeptidase Complex/chemistry,metabolism Saccharomyces cerevisiae/cytology,metabolism Substrate Specificity
Chemicals
Escherichia coli Proteins Immunoglobulins Polyubiquitin Proteasome Endopeptidase Complex
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Inobe Tomonao
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.
Fishbain Susan
Prakash Sumit
Matouschek Andreas
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.521
Published
2011-03-00
Epub
2011-00-30
Pages
161-7
Language
English
Region
United States
NLM ID
101231976
PMCID
PMC3129032
Subset
IM
Grants
NIGMS NIH HHS · R01 GM063004-09 · United States
NCI NIH HHS · U54CA143869 · United States
NCI NIH HHS · U54 CA143869-01 · United States
NIGMS NIH HHS · R01GM063004 · United States
NIGMS NIH HHS · R01 GM063004 · United States
NCI NIH HHS · U54 CA143869 · United States
External Links
PubMed source DOI: 10.1038/nchembio.521 PMC Full Text View journal details
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