The Structure and Assembly of Peptide Aggregates

Mount Holyoke College, South Hadley MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The aggregation of proteins and peptides is responsible for a number of diseases, including AIzheimer's and Parkinson's diseases. An understanding of the details of peptide aggregation mechanisms is prerequisite to understanding these diseases on the molecular level. This project will use a combination of biophysical techniques to describe the structure and assembly mechanism of a prion peptide and human gamma-D-crystallin, focusing on three specific aims: (1) dissecting the mechanism of beta-sheet formation by prion peptides in solution, using a combination of isotope-edited infrared (IR) spectroscopy, differential scanning calorimetry, and peptide design and modification; (2) exploring the morphology, strand alignment, and formation kinetics of prion peptide fiber through a combination of IR, electron microscopy, and atomic force microscopy; and (3) applying the isotope-edited IR technique to the study of protein aggregation in gamma-D-crystallin proteins. These studies will result in a comprehensive description of the aggregation process, from the initial conformational changes of individual polypeptides to the early stages of peptide aggregation to the formation of large fibrous precipitates. Such a thorough description of the aggregation process will lay a foundation for an improved understanding of many diseases at the molecular level, and also open the way for the development of new pharmaceutical strategies.