Interaction of the prion protein fragment PrP 185-206 with biological membranes: effect on membrane permeability.
Amyloids are proteinaceous aggregates related to the so-called conformational diseases, such as Alzheimer's and prion diseases. The cytotoxicity of amyloids may be related to the interaction of the amiloidogenic peptides or proteins with the cell membrane. In order to gain information on the physico-chemical effects of amyloids on membranes, we have studied the interaction of the human prion amyloidogenic fragment PrP 185-206 with negatively charged model membranes. The results show that the peptide causes the destabilization of the membrane, making it permeable to potassium ions and to charged organic compounds. This effect correlates with the interaction of the peptide with the membrane, causing a variation in the magnitude of the electrostatic surface and dipole membrane potentials. This effect on the electrostatic properties of the membranes may help explaining the observed permeability: a neutralization of the surface negative charge and a decrease of the inside-positive dipole potential would facilitate the translocation of positive ions. The structural analysis of the peptide in the presence of model membranes reveals that it adopts a predominantly unordered structure without any signs of amyloid formation. The results may be relevant in relation to the recently described cell toxic capacity of the peptide.
Sonkina
Sabina
S
Laboratory of Physical and Chemical methods, Institute of Bioorganic Chemistry of Science Academy, Mirzo Ulugbek, 83, Tashkent, Uzbekistan.
Tukhfatullina
Ilnor I
II
Benseny-Cases
Núria
N
Ionov
Maksim
M
Bryszewska
Maria
M
Salakhutdinov
Bakhtiyar A
BA
Cladera
Josep
J
D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D006801:Humans; D007477:Ions / Q000378:metabolism; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology; D055672:Static Electricity
D007477:Ions; D010446:Peptide Fragments; D011328:Prions