The prion diseases, which include Creutzfeldt-Jakob disease in humans, are a unique class of fatal neurodegenerative diseases believed to be caused by misfolding of a single protein, the prion protein (PrP).  PrP is linked to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor.  Interaction with the membrane may play a role in converting native PrP  to the misfolded state PrPSc. 
Robinson and Pinheiro studied the role of lipid membrane environment on PrP morphology and on growth of aggregation in two model membranes (1).  1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC, a zwitterionic phospholipid) and 1-palmitoyl-2-oleoyl-sn-glycero-2-phosphoserine (POPS, an anionic phospholipid) were each used to create lipid bilayers on the surface of freshly cleaved mica.  When a truncated form of PrP (90-231), which corresponds to the infectious core of PrP, was added to each of these lipid bilayers, atomic force microscopy and circular dichroism showed aggregation of PrP.  Interestingly, POPS, but not POPC, increases misfolded PrP content, increases the size of the aggregates, and creates a sponge-like appearance that disrupts the lipid bilayers, suggesting that anionic phospholipids present in membranes may accelerate PrP misfolding, and may act to direct PrP towards specific aggregation pathways that produce a distinct PrP morphology.

1.  Philip J. Robinson and Teresa J. Pinheiro. Phospholipid Composition of membranes Directs Prions Down Alternative Aggregation Pathways. Biophysical Journal. 98:1520-1528.

Reviewed by Justin Piro and T.Y. Chang, Department of Biochemistry, Dartmouth Medical School
Posted on:  10 May 2010