The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by:

Dylan Riggs, BCMB Graduate Student, UC Riverside 

Seminar Title: "Shining the Light on Aging and Isomers Using Photodissociation and Radical Chemistry"

Abstract: Deamidation of asparagine and isomerization of aspartic acid are spontaneous post-translational modifications associated with a growing list of human diseases. Although both processes are prevalent throughout the body, they are often overlooked because the resulting chemical modification is relatively minor and difficult to detect. Structural characterization is further complicated because both deamidation and isomerization produce four isomers of aspartic acid (L-Asp, D-Asp, L-isoAsp, and D-isoAsp). To address this analytical challenge, we utilized radical directed dissociation (RDD) in conjunction with mass spectrometry to identify and quantify all four isomers in a series of model peptides that were subjected to various deamidation conditions. We outlined intrinsic factors that govern the deamidation rate, and external factors that influence product outcomes. Following our initial studies, we have begun to explore how these unnatural amino acids contribute to protein dysfunction in isomerization hot-spots such as the amyloid plaques associated with Alzheimer’s Disease. To assess the role of isomerization in Alzheimer’s and other age-related diseases, we are characterizing isomerization rates and evaluating how isomers impact the fate of proteins in the brain. Preliminary results obtained via in vitro protease assays and live cell imaging indicate that isomers strongly influence the life-time of amyloid beta within neuroglia.