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Is PrP(106-126) Fragment Involved in the Membrane Activity of the Prion Protein?

[ Vol. 11 , Issue. 5 ]

Author(s):

Sonia Troeira Henriques and Miguel A.R.B. Castanho   Pages 326 - 333 ( 8 )

Abstract:


Prion diseases are a class of fatal neurodegenerative disorders that affect mammals and are characterized by their unique transmissibility and the nature of the infectious agent. When the physiological prion protein (PrPC) becomes corrupted (PrPSc) it accumulates in the brain, promoting infection and self-propagation via recruitment of PrPC. Although with identical sequence, PrPC and PrPSc differ in their physicochemical properties: PrPC is soluble, has an α-helical structure and is sensitive to enzymatic degradation, whereas PrPSc is insoluble, forms β-aggregates and is resistant to proteolysis. The fragment PrP(16-126) possess similar physicochemical and pathological properties to PrPsc, and therefore is commonly used as a model to study pathogenic effects. Although the pathogenicity of prion diseases is still unclear, strong evidences suggest that the cell membrane is relevant not only in infection and propagation of the disease but also in the manifestation of the clinical symptoms. In particular, the fragment PrP(106-126) has been implicated in the perturbation of the membranes and in the manifestation of Prion diseases. However, this is controversial. This review will discuss the effect of PrP(106-126) on the cell membrane based on its effect on model phospholipid bilayers. Different conditions were studied, including membrane charge, viscosity, lipid composition, pH, and ionic strength, revealing that PrP(106- 126) only interacts with lipid membranes at conditions with no physiological relevance. Such findings are here reviewed and correlated with the full-length protein effect.

Keywords:

Prion disease, PrP(106-126), Peptide-membrane interactions, model membranes

Affiliation:

Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Egas Moniz, Edificio Egas Moniz, 1649-028 Lisboa, Portugal; The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.



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