Journal Article

FZJ-2021-01244

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Zinc determines dynamical properties and aggregation kinetics of human insulin

Pounot, K. (Corresponding author) ; Grime, G. W. ; Longo, A. ; Zamponi, M.FZJ* ; Noferini, D.FZJ* ; Cristiglio, V. ; Seydel, T. ; Garman, E. F. ; Weik, M. ; Foderà, V. (Corresponding author) ; Schirò, G. (Corresponding author)

2021
Soc. Bethesda, Md.

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Please use a persistent id in citations: http://hdl.handle.net/2128/28048  doi:10.1016/j.bpj.2020.11.2280

Abstract: 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.

Keyword(s): Health and Life (1st) ; Biology (2nd)

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Contributing Institute(s):

1. JCNS-FRM-II (JCNS-FRM-II)
2. Neutronenstreuung (JCNS-1)
3. JCNS-4 (JCNS-4)
4. Heinz Maier-Leibnitz Zentrum (MLZ)

Research Program(s):

1. 6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ) (POF4-6G4) (POF4-6G4)
2. 632 - Materials – Quantum, Complex and Functional Materials (POF4-632) (POF4-632)

Experiment(s):

1. SPHERES: Backscattering spectrometer (NL6S)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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