Beta-Amyloid Fibril Binding to Phase Separated Lipid Rafts from Solution to Membranes

Published: 10 March 2020| Version 1 | DOI: 10.17632/ktrspy2swx.1
Contributors:
Kwan Cheng,
Sara Cheng

Description

Movies in animated GIF format showing the binding kinetics of human beta-amyloid fibrils of various sizes, derived from NMR structures (PDB: 2BEG), to phase separated lipid rafts consisting of saturated (DPPC) and unsaturated (DLPC) phospholipids, cholesterol (CHOL), head-group (C1-CHOL) or tail-group (P1-CHOL) modified cholesterol. These modified cholesterols mimic the oxidized cholesterols. The GM1 rafts contain asymmetrically distributed monosialotetrahexosylganglioside (GM1) clusters. These movies show coarse-grained (CG) MD simulations of fibril/raft complexes as described in Cheng et al. "Coarse-Grained MD Simulations Reveal Beta-Amyloid Fibrils of Various Sizes Bind to Interfacial Liquid-Ordered and Liquid-Disordered Regions in Phase Separated Lipid Rafts with Diverse Membrane-Bound Conformational States" Biophysical Chemistry 2020 in press (DOI: 10.1016/j.bpc.2020.106355). Each movie contains 500 frames, with a time step of 40 ns, spanning 0 to 20 microseconds of CG MD simulations. Periodic membrane structures along the z-axis are shown. The lipid acyl chains are not shown for clarity. The membrane-bound states include: C, T, N, I and L, and these states refer to the segment of the fibril that binds to the lipid membrane via the C-terminal, C-and N-termini, N-terminal, transmembrane-insertion along the C- and N-terminals, and loop region, respectively. 1. 01-CO-ABCD-2-0to20us-hgrs.gif A movie of a tetramer fibril (4 chains - ABCD) binding to a lipid raft (DPPC/DLPC/CHOL). The fibril starts from solution, binds to membrane at 4.2 microseconds, and establishes an equilibrated membrane-bound C-state. 2. 02-CO-ABCD-3-0to20us-hgrs.gif A movie of tetramer fibril (4 chains - ABCD) binding to a lipid raft (DPPC/DLPC/CHOL). The fibril starts from solution, binds to membrane at 0.4 microseconds, and establishes an equilibrated membrane-bound T-state. 3. 03-C1-ABC-3-0to20us-hgrs.gif A movie of a trimer fibril (3 chains - ABC) binding to a lipid raft (DPPC/DLPC/C1-CHOL). The fibril starts from solution, binds to membrane at 0.7 microseconds, and establishes an equilibrated membrane-bound N-state. 4. 04-P1-ABC-2-0to20us-hgrs.gif A movie of trimer fibril (3 chain - ABC) binding to a lipid raft (DPPC/DLPC/P1-CHOL). The fibril starts from solution, binds to membrane at 0.3 microseconds, and establishes an equilibrated membrane-bound I-state. 5. 05-GM-ABCD-1-0to20us-hgrs.gif A movie of a tetramer (ABCD) fibril binding to an asymmetrical lipid raft (DPPC/DLPC/CHOL/GM1). The fibril starts from solution, binds to membrane at 0.2 microseconds, and establishes an equilibrated membrane-bound C-state. 6. 06-GM-ABCD-2-0to2us-hgrs.gif A movie of a tetramer (ABCD) fibril binding to an asymmetrical lipid raft (DPPC/DLPC/CHOL/GM1). The fibril starts from solution, binds to asymmetric GM1 cluster at 1 microsecond, and establishes an equilibrated membrane-bound L-state.

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Institutions

Trinity University

Categories

Computational Biochemistry, Molecular Dynamics Simulations of Surface Phenomena, Glycolipids, Cholesterol, Lipid Raft, Binding Domain, Lipid Oxidation, Beta Amyloid in Alzheimer's Disease, Computational Molecular Modeling, Membrane Biophysics

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