Back to Search
Start Over
Adherent monomer-misfolded SOD1
- Source :
- PLoS ONE, PLoS ONE, Vol 3, Iss 10, p e3497 (2008)
- Publication Year :
- 2008
-
Abstract
- Background: Multiple cellular functions are compromised in amyotrophic lateral sclerosis (ALS). In familial ALS (FALS) with Cu/Zn superoxide dismutase (SOD1) mutations, the mechanisms by which the mutation in SOD1 leads to such a wide range of abnormalities remains elusive. Methodology/Principal Findings: To investigate underlying cellular conditions caused by the SOD1 mutation, we explored mutant SOD1-interacting proteins in the spinal cord of symptomatic transgenic mice expressing a mutant SOD1, SOD1 Leu126delTT with a FLAG sequence (DF mice). This gene product is structurally unable to form a functional homodimer. Tissues were obtained from both DF mice and disease-free mice expressing wild-type with FLAG SOD1 (WF mice). Both FLAG-tagged SOD1 and cross-linking proteins were enriched and subjected to a shotgun proteomic analysis. We identified 34 proteins (or protein subunits) in DF preparations, while in WF preparations, interactions were detected with only 4 proteins. Conclusions/Significance: These results indicate that disease-causing mutant SOD1 likely leads to inadequate proteinprotein interactions. This could be an early and crucial process in the pathogenesis of FALS.
- Subjects :
- Models, Molecular
Proteomics
Protein Folding
Microtubule-associated protein
Protein subunit
animal diseases
Mutant
SOD1
lcsh:Medicine
Mice, Transgenic
medicine.disease_cause
Neurological Disorders
Gene product
Superoxide dismutase
Mice
Superoxide Dismutase-1
Cerebellum
medicine
Animals
Protein Interaction Domains and Motifs
lcsh:Science
Genetics and Genomics/Medical Genetics
Mutation
Multidisciplinary
biology
Superoxide Dismutase
lcsh:R
Amyotrophic Lateral Sclerosis
nutritional and metabolic diseases
Molecular biology
nervous system diseases
Mice, Inbred C57BL
nervous system
Membrane protein
Spinal Cord
Biochemistry/Bioinformatics
biology.protein
lcsh:Q
Mutant Proteins
Biotechnology/Protein Chemistry and Proteomics
Protein Binding
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 3
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....bb1812d5cf174f075e6296cbbbd5494b