Phospholipid composition of membranes directs prions down alternative aggregation pathways
Robinson, Philip J. and Pinheiro, Teresa J. T.. (2010) Phospholipid composition of membranes directs prions down alternative aggregation pathways. Biophysical Journal, Vol.98 (No.8). pp. 1520-1528. ISSN 0006-3495Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.bpj.2009.12.4304
Prion diseases are neurodegenerative disorders of the central nervous system that are associated with the mis-folding of the prion protein (PrP). PrP is glycosylphosphatidylinositol-anchored, and therefore the hydrophobic membrane environment may influence the process of prion conversion. This study investigates how the morphology and mechanism of growth of prion aggregates on membranes are influenced by lipid composition. Atomic force microscopy is used to image the aggregation of prions on supported lipid bilayers composed of mixtures of the zwitterionic lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and the anionic lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS). Circular dichroism shows that PrP interactions with POPS membranes result in an increase in beta-sheet structure, whereas interactions with POPC do not influence PrP structure. Prion aggregation is observed on both zwitterionic and anionic membranes, and the morphology of the aggregates formed is dependent on the anionic phospholipid content of the membrane. The aggregates that form on POPC membranes have uniform dimensions and do not disrupt the lipid bilayer. The presence of POPS results in larger aggregates with a distinctive sponge-like morphology that are disruptive to membranes. These data provide detailed information on the aggregation mechanism of PrP on membranes, which can be described by classic models of growth.
|Item Type:||Journal Article|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)|
|Journal or Publication Title:||Biophysical Journal|
|Official Date:||21 April 2010|
|Number of Pages:||9|
|Page Range:||pp. 1520-1528|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)|
|Grant number:||BB/D524516/1 (BBSRC), 88/DTA19176|
Actions (login required)
Downloads per month over past year