Formation of low-dimensional crystalline nucleus region during insulin amyloidogenesis process

Biochemical and Biophysical Research Communications
Nadav AmdurskyGil Rosenman

Abstract

Insulin, as other amyloid proteins, can form amyloid fibrils at certain conditions. The self-assembled aggregation process of insulin can result in a variety of conformations, starting from small oligomers, going through various types of protofibrils, and finishing with bundles of fibrils. One of the most common consensuses among the various self-assembly processes that are suggested in the literature is the formation of an early stage nucleus conformation. Here we present an additional insight for the self-assembly process of insulin. We show that at the early lag phase of the process (prior to fibril formation) the insulin monomers self-assemble into ordered nanostructures. The most notable feature of this early self-assembly process is the formation of nanocrystalline nucleus regions with a strongly bound electron-hole confinement, which also change the secondary structure of the protein. Each step in the self-assembly process is characterized by an optical spectroscopic signature, and possesses a narrow size distribution. By following the spectroscopic signature we can measure the potency of amyloid fibrils inhibitors already at the lag phase. We further demonstrate it by the use of epigallocatechin gallate, a known inhibit...Continue Reading

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Citations

Mar 31, 2012·Physical Chemistry Chemical Physics : PCCP·Amir HandelmanGil Rosenman
Nov 17, 2015·The Journal of Physical Chemistry. B·Narendra Kumar MishraSandeep Verma
Jan 23, 2014·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Anita D'SouzaAhmet Dogan
Apr 19, 2016·Diabetic Medicine : a Journal of the British Diabetic Association·A ManglaJ J Jiang
Mar 17, 2018·Biochemistry. Biokhimii︠a︡·O M SelivanovaO V Galzitskaya
Nov 15, 2016·Soft Matter·Rhiannon C G CreaseySaul J B Tendler
Jul 25, 2020·Skeletal Radiology·Sohil S DesaiMotasem Al Maaieh
Sep 28, 2013·Molecular Pharmaceutics·Narendra Kumar MishraSandeep Verma
Nov 24, 2021·Journal of Chemical Theory and Computation·Rit Pratik Mishra, Gaurav Goel

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