A Hybrid Structural Method for Investigating Low Molecular Weight Oligomeric Structures of Amyloid Beta

Abstract

Spurred in part by the failure of recent therapeutics targeting amyloid β plaques in Alzheimer's Disease (AD), attention is increasingly turning to the oligomeric forms of this peptide that form early in the aggregation process. However, while numerous amyloid β fibril structures have been characterized, primarily by NMR spectroscopy and cryo-EM, obtaining structural information on the low molecular weight forms of amyloid β that presumably precede and/or seed fibril formation has proved challenging. These transient forms are heterogeneous, and depend heavily on experimental conditions such as buffer, temperature, concentration, and degree of quiescence during measurement. Here, we present the concept for a new approach to delineating structural features of early-stage low molecular weight amyloid β oligomers, using a solvent accessibility assay in conjunction with simultaneous fluorescence measurements.

Structural Investigation of Therapeutic Antibodies Using Hydroxyl Radical Protein Footprinting Methods

“…In practice, HRPF experiments are most commonly carried out with phosphate buffer or Na-cacodylate buffer, though some progress has been made with high-flux-density beamlines or higher-yield photolysis systems for overcoming scavenging effects. One advantage of the method is that with modern implementations of sample delivery, it becomes possible to couple sample delivery with additional characterization, such as spectroscopy [ 53 ], or with sample pre-processing, such as inline size-exclusion chromatography [ 54 ].…”