An Integrated Structural Biology Dataset Reveals Metal-Protein and Protein-Protein Interactions of Critical Importance for Amyloid Formation

摘要

Amyloidosis is a pathogenic form of protein aggregation associated with a number of diseases including Alzheimer's and Parkinson's disease. While studies using conventional technologies have yielded important structural insights and some understanding of the molecular processes underlying aggregation, the application of these insights to amyloidogenesis at the cellular level has been less successful, suggesting a discrepancy between our molecular-level understanding and amyloidosis in vivo. Our approach involves the integration of ion mobility-mass spectrometry (IM-MS), nuclear magnetic resonance (NMR) spectroscopy, and other chemical biology-derived datasets in an attempt to assess the complete interaction network involved in amyloid formation. In this study, we focus on the interactions between several amyloidogenic peptides, including Amyloid Beta (A(beta)) and Islet Amyloid Polypeptides (IAPP), with metals and proteins.