Insulin fibrillation: The influence and coordination of Zn2+

Publication: Research - peer-reviewJournal article – Annual report year: 2017

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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.
Original languageEnglish
JournalJournal of Structural Biology
Volume199
Issue number1
Pages (from-to)27-38
ISSN1047-8477
DOIs
StatePublished - 2017
CitationsWeb of Science® Times Cited: 0

    Keywords

  • Amyloid, EXAFS, Fibre diffraction, Fibrillation, Insulin, TEM, Thioflavin T, XAS, Zinc
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