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Electrostatic interactions between negatively charged phospolipid membranes and SOD1 protein : Effect of charge changing fALS mutations
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- Byström, Roberth, 1971- (author)
- Umeå universitet,Kemiska institutionen
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- Aisenbrey, Christopher (author)
- Umeå universitet,Kemiska institutionen
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- Oliveberg, Mikael (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories of Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden
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Abstract
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- The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is closely connected to single site mutations of the Cu/Zn superoxide dismutase (SOD1) protein, whose pathological conversion into misfolded aggregates is a hallmark of ALS. To explore the impact of protein net charge changing ALS relevant SOD1 mutations on their ability to interact with neuronal membranes and the consequences for their folding behaviour, we studied by circular dichroism the conformational changes of the SOD1pWT, SOD1N86D and SOD1N86K species in their apo-state in the presence of increasing amounts of negatively charged lipid bilayers.. The results clearly indicate an electrostatically driven association process, where the association event induces a pronounced increase in the helical character of the pWT and the N86D species, characterized by long patient survival times. To the opposite, the charge reducing N86K mutation shows more pronounced β-like features in the presence of membranes in comparison to the other two species; an observation which most likely reflects its reduced stability in its apo-state in combination with a very fast ALS progression.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Biochemistry
- Biokemi
Publication and Content Type
- pop (subject category)
- ovr (subject category)
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