Insulin fibrillation: The influence and coordination of Zn2

Journal of Structural Biology
Christian Grundahl FrankærPernille Harris

Abstract

Protein amyloid fibrillation is obtaining much focus because it is connected with amyloid-related human diseases such as Alzheimer's disease, diabetes mellitus type 2, or Parkinson's disease. The influence of metal ions on the fibrillation process and whether it is implemented in the amyloid fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy. The results were validated with fibre diffraction, Transmission Electron Microscopy and Thioflavin T fluorescence measurements. It is well-known that Zn2+ ions coordinate and stabilize the hexameric forms of insulin. However, this study is the first to show that zinc indeed binds to the insulin fibrils. Furthermore, zinc influences the kinetics and the morphology of the fibrils. It also shows that zinc coordinates to histidine residues in an environment, which is similar to the coordination seen in the insulin R6 hexamers, where three histidine residues and a chloride ion is coordinating the zinc.

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Citations

Dec 6, 2018·Physical Chemistry Chemical Physics : PCCP·Deliang ChenXiaolin Fan
Apr 6, 2019·Acta Crystallographica. Section D, Structural Biology·Line A RybergPernille Harris
Oct 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Monika SwiontekBeata Kolesinska
Sep 30, 2020·Chemical Communications : Chem Comm·Mohsen AkbarianVladimir N Uversky
Oct 3, 2018·Metallomics : Integrated Biometal Science·Michael J StevensonMarie C Heffern
Mar 31, 2019·Biochemistry. Biokhimii︠a︡·A K SurinO V Galzitskaya
Feb 6, 2021·Biophysical Journal·Kevin PounotGiorgio Schirò
Jun 12, 2021·Journal of Diabetes Science and Technology·Marc B TarabanYihua Bruce Yu
Jun 19, 2021·IScience·Meghomukta MukherjeePartha Chakrabarti

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