Dynamic conformations of amyloid peptides related to different diseases and discern their common
Many human diseases such as Alzheimer’s disease, type II diabetes, Parkinson’s disease, spongiform encephalopathies, etc are highly related with a common pathogenic progress, called “amyloidogenesis”. Interestingly, many amyloidogenic peptides are intrinsically disordered in solution and they undergo structural conversions between random coil or helical conformations and β-strands-rich structures which are prone to stabilize the aggregates. Among more than twenty human degenerative diseases having the ability to form amyloid deposits associated with several human pathologenetic diseases, there are two of them: the type 2 diabetes, associated to the Islet Amyloid Polypeptide (IAPP) and the Alzheimer disease involved the Amyloid β-peptide (Aβ). IAPP is a 37-residues peptide hormone co-secreted with insulin from the pancreatic β-cells and Aβ affects brain tissues and its two most common alloforms are 40 and 42 residues in length. The aggregation mechanism of these peptides still remains unclear in detail but a general scheme has revealed that different types of soluble amyloid oligomers have a common structure and share a common mechanism of toxicity. In solution, these disordered peptides dynamically visit various metastable conformations, one of them being rich in β-strands structures, which favor the peptides oligomerization, through β-strand/β-strand interactions and eventually the fibrils formations. This research aims to compare the dynamic conformations of amyloid peptides related to different diseases and discern their common and different structural and binding properties.