| Autor: |
Galvagnion C; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark. celine.galvagnion@sund.ku.dk., Barclay A; Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark., Makasewicz K; Division of Physical Chemistry, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100, Lund, Sweden., Marlet FR; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark. celine.galvagnion@sund.ku.dk., Moulin M; Institut Laue-Langevin, 71 avenue des Martyrs, 38042 Grenoble, France., Devos JM; Institut Laue-Langevin, 71 avenue des Martyrs, 38042 Grenoble, France., Linse S; Department of Biochemistry and Structural Biology, Lund University, SE22100 Lund, Sweden., Martel A; Institut Laue-Langevin, 71 avenue des Martyrs, 38042 Grenoble, France., Porcar L; Institut Laue-Langevin, 71 avenue des Martyrs, 38042 Grenoble, France., Sparr E; Division of Physical Chemistry, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100, Lund, Sweden., Pedersen MC; Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark., Roosen-Runge F; Division of Physical Chemistry, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100, Lund, Sweden.; Department of Biomedical Sciences and Biofilms Research Center for Biointerfaces, Malmö University, Malmö, Sweden., Arleth L; Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark., Buell AK; Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark. alebu@dtu.dk. |
| Abstrakt: |
The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact mechanism of this acceleration is still mostly unclear. Here we use a range of scattering methods, such as dynamic light scattering (DLS) and small angle X-ray and neutron scattering (SAXS and SANS) to obtain structural information on the binding of α-synuclein to model membranes formed from negatively charged lipids and their co-assembly into amyloid fibrils. We find that the model membranes take an active role in the reaction. The binding of α synuclein to the model membranes immediately induces a major structural change in the lipid assembly, which leads to a break-up into small and mostly disc- or rod-like lipid-protein particles. This transition can be reversed by temperature changes or proteolytic protein removal. Incubation of the small lipid-α-synuclein particles for several hours, however, leads to amyloid fibril formation, whereby the lipids are incorporated into the amyloid fibrils. |
