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Identification of the iduronate-2-sulfatase proteome in wild-type mouse brain
- Source :
- Heliyon, Vol 5, Iss 5, Pp e01667-(2019), Heliyon
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Iduronate-2-sulfatase (IDS) is a lysosomal enzyme involved in the metabolism of the glycosaminoglycans heparan (HS) and dermatan (DS) sulfate. Mutations on IDS gene produce mucopolysaccharidosis II (MPS II), characterized by the lysosomal accumulation of HS and DS, leading to severe damage of the central nervous system (CNS) and other tissues. In this study, we used a neurochemistry and proteomic approaches to identify the brain distribution of IDS and its interacting proteins on wild-type mouse brain. IDS immunoreactivity showed a robust staining throughout the entire brain, suggesting an intracellular reactivity in nerve cells and astrocytes. By using affinity purification and mass spectrometry we identified 187 putative IDS partners-proteins, mainly hydrolases, cytoskeletal proteins, transporters, transferases, oxidoreductases, nucleic acid binding proteins, membrane traffic proteins, chaperons and enzyme modulators, among others. The interactions with some of these proteins were predicted by using bioinformatics tools and confirmed by co-immunoprecipitation analysis and Blue Native PAGE. In addition, we identified cytosolic IDS-complexes containing proteins from predicted highly connected nodes (hubs), with molecular functions including catalytic activity, redox balance, binding, transport, receptor activity and structural molecule activity. The proteins identified in this study would provide new insights about IDS physiological role into the CNS and its potential role in the brain-specific protein networks.
- Subjects :
- 0301 basic medicine
Cell biology
Bioinformatics
DNA-binding protein
Biochemistry
Article
Computational biology
03 medical and health sciences
0302 clinical medicine
Affinity chromatography
lcsh:Social sciences (General)
Receptor
Cytoskeleton
lcsh:Science (General)
chemistry.chemical_classification
Multidisciplinary
Iduronate-2-sulfatase
Cytosol
030104 developmental biology
Enzyme
chemistry
Proteome
lcsh:H1-99
030217 neurology & neurosurgery
Biotechnology
lcsh:Q1-390
Subjects
Details
- Language :
- English
- ISSN :
- 24058440
- Volume :
- 5
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Heliyon
- Accession number :
- edsair.doi.dedup.....36ec059c4243b6eeacd117ed4b636299