Skip to Main content Skip to Navigation
Journal articles

Can Arginine Inhibit Insulin Aggregation? A Combined Protein Crystallography, Capillary Electrophoresis, and Molecular Simulation Study

Abstract : The oligomeric state of the storage form of human insulin in the pancreas, which may be affected by several endogenous components of β-cell storage granules such as arginine, is not known. Here, the effect of arginine on insulin oligomerization is investigated independently by protein crystallography, molecular dynamics simulations, and capillary electrophoresis. The combined results point to a strong effect of ionic strength on insulin assembly. Molecular simulations and electrophoretic measurements at low/mM salt concentrations show no significant effect of arginine on insulin aggregation. In contrast, crystallographic data at high/molar ionic strength indicate inhibition of insulin hexamerization by arginine due to its binding at the site relevant for intermolecular contacts, which was also observed in MD simulations. Our results thus bracket the in vivo situation in pancreatic β-cell storage granules, where the ionic strength is estimated to be in the hundreds of millimolar to submolar range. The present findings add to a molecular understanding of in vivo insulin oligomerization and storage, with additional implications for insulin stability in arginine-rich injections.
Complete list of metadatas

Cited literature [59 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02309468
Contributor : Elise Duboué-Dijon <>
Submitted on : Wednesday, October 9, 2019 - 12:11:08 PM
Last modification on : Thursday, November 19, 2020 - 11:02:01 AM

File

paper303.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Kryštof Březina, Elise Duboue-Dijon, Vladimír Palivec, Jiří Jiráček, Tomáš Křížek, et al.. Can Arginine Inhibit Insulin Aggregation? A Combined Protein Crystallography, Capillary Electrophoresis, and Molecular Simulation Study. Journal of Physical Chemistry B, American Chemical Society, 2018, 122 (44), pp.10069-10076. ⟨10.1021/acs.jpcb.8b06557⟩. ⟨hal-02309468⟩

Share

Metrics

Record views

317

Files downloads

814