Exposure of Aggregation-Prone Segments is the Requirement for Amyloid Fibril Formation

Title:Exposure of Aggregation-Prone Segments is the Requirement for Amyloid Fibril Formation

Volume: 19 Issue: 10

Author(s): Shreya Pramanik and Basir Ahmad*

Affiliation:

• Biophysical Chemistry & Structural Biology laboratory, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai campus, Vidyanagari, Kalina, Mumbai,India

Keywords: Native like state, aggregation precursor state, amyloid fibril, kinetic trap, protein misfolding, energy landscape.

Abstract: Arranging into well-organized fibrillar aggregate, commonly known as amyloid fibril is an inherent property of any polypeptide chain. Amyloid fibrils are associated with a number of severe human pathologies like the Alzheimer's disease, Parkinson's disease, type2 diabetes and many more. Recent studies suggest that most of the fibrils are inert and extremely stable, thus could be used for the bionanotechnological applications. As the native state is protected by evolution from aggregation under physiological condition, understanding the structure of aggregation precursor state (APS) will be of extreme importance to decode mechanism of its formation and prevention. This review article includes the recent studies of identification and characterization of possible conformations of proteins which can act as APS. The literature regarding the research in this field revealed that any conformation ranging from native-like state to completely unfolded state could be an APS. The structural characteristics of the APS depend on the protein and on its surrounding environment. From this review of literatures, we conclude that exposure of aggregation-prone segments is the requirement for amyloid fibril formation and the amyloid state seems to be the most stable known physical state of the proteins. This means all conformations of proteins with exposed aggregation-prone segments can promote intermolecular interactions and channel to amyloid fibril pathway to acquire their minimum energy state.

Cite this article as:

Pramanik Shreya and Ahmad Basir *, Exposure of Aggregation-Prone Segments is the Requirement for Amyloid Fibril Formation, Current Protein & Peptide Science 2018; 19 (10) . https://dx.doi.org/10.2174/1389203719666180521091647