Physics (Internal)

Insights into amyloid β-protein self–assembly: Specificity versus universality

This event is part of the Biophysics/Condensed Matter Seminar Series.

Abstract: Aberrant protein aggregation is at the core of many age–triggered dis- eases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, amy- otrophic lateral sclerosis, type II diabetes, systemic amyloidoses, and others. These amyloid proteins do not share any obvious aspects of the primary struc- ture yet they self–assemble into cytotoxic low–molecular weight oligomers and form fibrils with a common cross-β structure. Amyloid β-protein (Aβ) assembly plays a central role in Alzheimer’s disease (AD). I will describe our recent computational and experimental studies that provide insights into oligomer structures of several Aβ isoforms and thereby elucidate a possible structural basis of Aβ oligomer toxicity. I will also present a minimal model of self–assembly, which reveals unexpected diversity and complexity of assem- bly pathways and structures characteristic for amyloidogenic proteins and show that a single model parameter can be meaningfully mapped onto the sequence of several amyloidogenic proteins, thus providing a theoretical basis for understanding protein assembly pathways.