This title appears in the Scientific Report :
2021
Please use the identifier:
http://hdl.handle.net/2128/28048 in citations.
Please use the identifier: http://dx.doi.org/10.1016/j.bpj.2020.11.2280 in citations.
Zinc determines dynamical properties and aggregation kinetics of human insulin
Zinc determines dynamical properties and aggregation kinetics of human insulin
Protein 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...
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Personal Name(s): | Pounot, Kevin (Corresponding author) |
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Grime, Geoffrey W. / Longo, Alessandro / Zamponi, Michaela / Noferini, Daria / Cristiglio, Viviana / Seydel, Tilo / Garman, Elspeth F. / Weik, Martin / Foderà, Vito (Corresponding author) / Schirò, Giorgio (Corresponding author) | |
Contributing Institute: |
JCNS-FRM-II; JCNS-FRM-II Heinz Maier-Leibnitz Zentrum; MLZ JCNS-4; JCNS-4 Neutronenstreuung; JCNS-1 |
Published in: | Biophysical journal, 120 (2021) 5, S. 886 |
Imprint: |
Bethesda, Md.
Soc.
2021
|
DOI: |
10.1016/j.bpj.2020.11.2280 |
Document Type: |
Journal Article |
Research Program: |
Materials – Quantum, Complex and Functional Materials Jülich Centre for Neutron Research (JCNS) (FZJ) |
Subject (ZB): | |
Link: |
Published on 2021-02-03. Available in OpenAccess from 2022-02-03. |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1016/j.bpj.2020.11.2280 in citations.
Protein 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. |