Prof. Jie Zheng, University of Akron Department of Chemical and Biomolecular Engineering
January 31, 2012
11:00 AM - 12:00 PM
Molecular Insights into Amyloid Oligomers and their Interactions with Model Membranes
Abstract:
The aggregation of monomeric proteins/peptides to form ordered amyloid oligomers/fibrils is a pathogenic hallmark of many degenerative diseases including Alzheimer’s, Parkinson’s, and prion diseases. Despite of significant progress, oligomeric structures and associated toxicity at the very early stage of aggregation remain unclear. Structural knowledge of these oligomers is essential for understanding the pathology of amyloidoses and for the rational design of drugs against amyloid diseases. This talk will cover our recent works in three aspects. (i) We identify a series of atomic structures of amyloid oligomers with different sequences (ABeta;, hIAPP, GNNQQNY, and K3) and structural morphologies (micelles, annulars, triangulars, globulomers, and linears), delineate several common features in amyloid structures, and illustrate aggregation driving forces that stabilize these oligomeric structures. (ii) More importantly, we further examine the interactions of amyloid oligomers with lipid bilayers to examine membrane-damage mechanisms by varying oligomeric morphology, lipid compositions, cholesterol contents, and position and orientation of ABeta; relative to lipid bilayers. Two postulated mechanisms of membrane damage (membrane thinning vs. ion channel) associated with amyloid toxicity are discussed. (iii) In addition, due to the complex nature of cell membranes, we also alternatively employ self-assembled monolayers (SAMs) as model systems to study the aggregation and conformational changes of ABeta; peptides using an integrated simulation and experimental approach. The complementary results from simulations and experiments reveal different ABeta; adsorption, structural transition, and aggregation scenarios on the SAMs, providing parallel insights into the understanding of ABeta; structure and aggregation on cell membrane.
Date posted
Jun 17, 2019
Date updated
Jun 17, 2019