Mechanistic perspective and functional activity of insulin in amylin aggregation

Chemical Science
Michal BaramYifat Miller

Abstract

Insulin is a key regulatory polypeptide that is secreted from pancreatic β-cells and has several important effects on the synthesis of lipids, regulation of enzymatic activities, blood glucose levels and the prevention of hyperglycemia. Insulin was demonstrated to self-assemble into ordered amyloid fibrils upon repeated injections, although the possible biological significance of the supramolecular structures is enigmatic. Amylin is also an amyloidogenic polypeptide that is secreted from pancreatic β-cells and plays an important role in glycemic regulation preventing post-prandial spikes in blood glucose levels. These two amyloidogenic proteins are secreted together from the pancreas and have the ability to interact and produce insulin-amylin aggregates. So far, the molecular architecture of insulin-amylin complexes at the atomic resolution has been unknown. The current work identifies for the first time the specific π-π interactions between Y16 in insulin and F19 in amylin that contribute to the stability of the insulin-amylin complex, by using experimental and molecular modeling techniques. We performed additional experiments that verify the functional activity of insulin in amylin aggregation. Our findings illustrate for the...Continue Reading

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Citations

Jul 9, 2020·Nanoscale·Nicholas AndrikopoulosPu Chun Ke
Aug 5, 2020·Chemical Communications : Chem Comm·Yuko P Y LamPeter B O'Connor
Jan 8, 2021·Journal of Molecular Modeling·Rafael B Frigori, Fabio Rodrigues
Feb 4, 2021·ACS Chemical Neuroscience·Yehong GongQingwen Zhang
Dec 4, 2019·Journal of Chemical Information and Modeling·Cecilia Prudkin-SilvaFernando L Barroso da Silva
Mar 6, 2021·Molecular and Cellular Biochemistry·Carla P Barragán-ÁlvarezNestor E Díaz-Martínez
Jun 19, 2021·IScience·Meghomukta MukherjeePartha Chakrabarti
Jul 3, 2019·Journal of Chemical Information and Modeling·Antonio Vitale, Velia Minicozzi

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Methods Mentioned

BETA
peptide array
peptide-array
fluorescence assay

Software Mentioned

NAMD

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