Talk in Chemistry: Conformational Excursions of Proteins Heading to Nanoscale Amyloid Assembly

 Conformational Excursions of Proteins Heading to Nanoscale Amyloid Assembly
 Mily Bhattacharya
 Indian Institute of Science Education and Research (IISER) Mohali, Punjab, India.

Proteins are biopolymers which act as efficient miniature engines in the living systems and carry out a multitude of extremely important physiological functions in their correctly folded form. However, changes in solution conditions and/or mutations in the protein sequence result in the formation of aberrantly-folded or misfolded states of the protein that subsequently undergo self-assembly and accumulate as amyloid aggregates. Amyloid aggregates are implicated in a plethora of debilitating human disorders such as Alzheimer’s and Parkinson’s diseases, Prion diseases, liver cirrhosis, type II diabetes etc. Studies have revealed that the transition from a normal functional protein to an abnormal, misfolded form involves a major conformational change that serves as the key step in protein aggregation. However, a complete understanding of protein aggregation and amyloid assembly, especially the onset and mechanistic details of initial events, still remains elusive. In this talk, I will discuss about our efforts in understanding the structural and dynamical aspects of a few model proteins possessing diverse native structures under both monomeric and aggregated conditions using a host of biophysical tools involving fluorescence and Raman spectroscopy, circular dichroism, light scattering, atomic force microscopy and near-field scanning optical microscopy. Our data revealed that the formation of soluble oligomers precedes the profound conformational switch that leads to amyloid aggregates with diverse nanoscale morphologies. These results will be useful in the chemical biology approach of anti-amyloid therapeutics to combat amyloid disorders.

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