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Title [sv]
Proteinernas Felveckning/Aggregering på membrae ytor: inne i en cell.
Title [en]
Protein Misfolding/Aggregation at Membrane Surfaces: Inside the Cell
Abstract [sv]
This project aims to provide molecular insight into membrane induced accelerated aggregation of amyloidogenic proteins under macromolecular crowding conditions, mimicking the situation inside cells. We will use a cross-disciplinary approach with Abeta as model system, to describe the fundamental features of protein misfolding and aggregation under conditions where a three-dimensional crowded environment competes with membrane surfaces of a two-dimensional nature; a process we recently started to study (JACS 129 (2007) 14848-). Using biophysical methods including solid state NMR as main technique we will structurally describe the occuring protein aggregates and protein-lipid complexes; information essential for a molecular understanding of the occurring folding pathways and their dependence on the target membrane (focus on mitochondrial ones) and crowding conditions. We will also correlate protein assemblies generated at different stages, to their intracellular exerted toxicity, using an intracellular mitochondria based assay. This will provide essential information about the mechanism and toxic impact of membrane-mediated Abeta-aggregation in a cell-like environment. The methodological platform, developed with A-beta, will then be used to further investigate the folding behaviour of the intracellular Cu-Zn superoxide dismutase 1 (SOD1) involved in amyotrophic lateral sclerosis (ALS) under these conditions and the toxic consequences.
Principal InvestigatorGröbner, Gerhard
Coordinating organisation
Umeå University
Funder
Period
2010-01-01 － 2012-12-31
Identifiers
DiVA, id: project:912Project, id: 2009-03712_VR

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