Source:http://linkedlifedata.com/resource/pubmed/id/16441516
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2006-2-15
|
| pubmed:abstractText |
Superoxide dismutase 1 (SOD1) proteins harboring mutations linked to familial amyotrophic lateral sclerosis (FALS) uniformly show heightened potential to form high molecular weight structures. Here, we examine the domains of SOD1 that are involved in forming these structures (aggregates) and study the role of intra- and intermolecular disulfide bonds. An analysis of disease mutations identified to date reveals a non-random distribution with predominant occurrence at residues within highly conserved beta-strands or at highly conserved residues in loop domains. Using a cell transfection assay for aggregation, we determined that no single domain in SOD1 is indispensable in the formation of sedimentable aggregates, suggesting multiple potential motifs in the protein mediate non-native interactions. By a cell-free aggregation assay, analysis of transgenic mouse tissues, and mutagenesis approaches, we found evidence that redox conditions may modulate SOD1 aggregation; reduction of the native intramolecular disulfide bonds may predispose SOD1 to unfolding and aggregation, whereas non-native intermolecular disulfide linkages may help stabilize aggregates in vivo. The results suggest a possible mechanism for diversity in the structures formed by different SOD1 mutants, and define a potential contribution of redox conditions to SOD1 aggregation.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0022-3042
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
96
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1277-88
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:16441516-Age Factors,
pubmed-meshheading:16441516-Amino Acid Motifs,
pubmed-meshheading:16441516-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:16441516-Animals,
pubmed-meshheading:16441516-Blotting, Western,
pubmed-meshheading:16441516-Cell Fractionation,
pubmed-meshheading:16441516-Cysteine,
pubmed-meshheading:16441516-Dimerization,
pubmed-meshheading:16441516-Disease Models, Animal,
pubmed-meshheading:16441516-Disulfides,
pubmed-meshheading:16441516-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:16441516-Humans,
pubmed-meshheading:16441516-Mice,
pubmed-meshheading:16441516-Mice, Inbred C57BL,
pubmed-meshheading:16441516-Mice, Transgenic,
pubmed-meshheading:16441516-Mutagenesis,
pubmed-meshheading:16441516-Protein Binding,
pubmed-meshheading:16441516-Protein Folding,
pubmed-meshheading:16441516-Spinal Cord,
pubmed-meshheading:16441516-Superoxide Dismutase,
pubmed-meshheading:16441516-Transfection
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
Mapping superoxide dismutase 1 domains of non-native interaction: roles of intra- and intermolecular disulfide bonding in aggregation.
|
| pubmed:affiliation |
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|