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  • Requirements for mutant and wild-type prion protein misfolding in vitro.

Requirements for mutant and wild-type prion protein misfolding in vitro.

Biochemistry (2015-01-15)
Geoffrey P Noble, Daniel J Walsh, Michael B Miller, Walker S Jackson, Surachai Supattapone
ABSTRACT

Misfolding of the prion protein (PrP) plays a central role in the pathogenesis of infectious, sporadic, and inherited prion diseases. Here we use a chemically defined prion propagation system to study misfolding of the pathogenic PrP mutant D177N in vitro. This mutation causes PrP to misfold spontaneously in the absence of cofactor molecules in a process dependent on time, temperature, pH, and intermittent sonication. Spontaneously misfolded mutant PrP is able to template its unique conformation onto wild-type PrP substrate in a process that requires a phospholipid activity distinct from that required for the propagation of infectious prions. Similar results were obtained with a second pathogenic PrP mutant, E199K, but not with the polymorphic substitution M128V. Moreover, wild-type PrP inhibits mutant PrP misfolding in a dose-dependent manner, and cofactor molecules can antagonize this effect. These studies suggest that interactions between mutant PrP, wild-type PrP, and other cellular factors may control the rate of PrP misfolding in inherited prion diseases.

MATERIALS
Product Number
Brand
Product Description

Avanti
C18(Plasm)-18:1 PE, 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphoethanolamine, powder
Avanti
Brain PC, Avanti Research - A Croda Brand 840053P, powder
Avanti
C18(Plasm)-18:1 PE, Avanti Research - A Croda Brand
Avanti
Brain PC, Avanti Research - A Croda Brand 840053C