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000890913 1001_ $$0P:(DE-HGF)0$$aPounot, Kevin$$b0$$eCorresponding author
000890913 245__ $$aZinc determines dynamical properties and aggregation kinetics of human insulin
000890913 260__ $$aBethesda, Md.$$bSoc.$$c2021
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000890913 520__ $$aProtein aggregation is a widespread process leading to deleterious consequences in the organism, with amyloid aggregates being important not only in biology but also for drug design and biomaterial production. Insulin is a protein largely used in diabetes treatment, and its amyloid aggregation is at the basis of the so-called insulin-derived amyloidosis. Here, we uncover the major role of zinc in both insulin dynamics and aggregation kinetics at low pH, in which the formation of different amyloid superstructures (fibrils and spherulites) can be thermally induced. Amyloid aggregation is accompanied by zinc release and the suppression of water-sustained insulin dynamics, as shown by particle-induced x-ray emission and x-ray absorption spectroscopy and by neutron spectroscopy, respectively. Our study shows that zinc binding stabilizes the native form of insulin by facilitating hydration of this hydrophobic protein and suggests that introducing new binding sites for zinc can improve insulin stability and tune its aggregation propensity.
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000890913 7001_ $$0P:(DE-HGF)0$$aGrime, Geoffrey W.$$b1
000890913 7001_ $$0P:(DE-HGF)0$$aLongo, Alessandro$$b2
000890913 7001_ $$0P:(DE-Juel1)131056$$aZamponi, Michaela$$b3$$ufzj
000890913 7001_ $$0P:(DE-Juel1)165355$$aNoferini, Daria$$b4$$ufzj
000890913 7001_ $$0P:(DE-HGF)0$$aCristiglio, Viviana$$b5
000890913 7001_ $$0P:(DE-HGF)0$$aSeydel, Tilo$$b6
000890913 7001_ $$0P:(DE-HGF)0$$aGarman, Elspeth F.$$b7
000890913 7001_ $$0P:(DE-HGF)0$$aWeik, Martin$$b8
000890913 7001_ $$0P:(DE-HGF)0$$aFoderà, Vito$$b9$$eCorresponding author
000890913 7001_ $$0P:(DE-HGF)0$$aSchirò, Giorgio$$b10$$eCorresponding author
000890913 773__ $$0PERI:(DE-600)1477214-0$$a10.1016/j.bpj.2020.11.2280$$gp. S0006349521000862$$n5$$p886$$tBiophysical journal$$v120$$x0006-3495$$y2021
000890913 8564_ $$uhttps://juser.fz-juelich.de/record/890913/files/zamponi_Pounot_final.pdf$$yPublished on 2021-02-03. Available in OpenAccess from 2022-02-03.
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