Linked Life Data

15016805

Source:http://linkedlifedata.com/resource/pubmed/id/15016805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2004-5-10
pubmed:abstractText
Proteasomes denature folded protein substrates and thread them through a narrow pore that leads to the sequestered sites of proteolysis. Whether a protein substrate initiates insertion from its N or C terminus or in a random orientation has not been determined for any natural substrate. We used the labile enzyme ornithine decarboxylase (ODC), which is recognized by the proteasome via a 37-residue C-terminal tag, to answer this question. Three independent approaches were used to assess orientation as follows. 1) The 461-residue ODC protein chain was interrupted at position 305. The C-terminal fragment was degraded by purified proteasomes, but because processivity requires continuity of the polypeptide chain, the N-terminal fragment was spared. 2) A proteasome-inhibitory viral sequence prevented degradation when introduced near the C terminus but not when inserted elsewhere in ODC. 3) A bulky tightly folded protein obstructed in vivo degradation most effectively when positioned near the C terminus. These data demonstrate that the proteasome initiates degradation of this native substrate at the C terminus. The co-localization of entry site and degradation tag to the ODC C terminus suggests that recognition tags determine the site for initiating entry. Flexibility of a polypeptide terminus may promote the initiation of degradation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20959-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15016805-Animals, pubmed-meshheading:15016805-Cycloheximide, pubmed-meshheading:15016805-Cysteine Endopeptidases, pubmed-meshheading:15016805-Genetic Vectors, pubmed-meshheading:15016805-Methotrexate, pubmed-meshheading:15016805-Mice, pubmed-meshheading:15016805-Multienzyme Complexes, pubmed-meshheading:15016805-Mutagenesis, Insertional, pubmed-meshheading:15016805-Ornithine Decarboxylase, pubmed-meshheading:15016805-Peptide Fragments, pubmed-meshheading:15016805-Plasmids, pubmed-meshheading:15016805-Polymerase Chain Reaction, pubmed-meshheading:15016805-Proteasome Endopeptidase Complex, pubmed-meshheading:15016805-Protein Denaturation, pubmed-meshheading:15016805-Recombinant Fusion Proteins, pubmed-meshheading:15016805-Saccharomyces cerevisiae, pubmed-meshheading:15016805-Substrate Specificity
pubmed:year
2004
pubmed:articleTitle
Proteasomes begin ornithine decarboxylase digestion at the C terminus.
pubmed:affiliation
Department of Microbiology and Immunology, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.