Chemistry
Document Type
Article
Abstract
Insulin-degrading enzyme (IDE) is an evolutionarily conserved ubiquitous zinc metalloprotease implicated in the efficient degradation of insulin monomer. However, IDE also degrades monomers of amyloidogenic peptides associated with disease, complicating the development of IDE inhibitors. In this work, we investigated the effects of the lipid composition of membranes on the IDE-dependent degradation of insulin. Kinetic analysis based on chromatography and insulin's helical circular dichroic signal showed that the presence of anionic lipids in membranes enhances IDE's activity toward insulin. Using NMR spectroscopy, we discovered that exchange broadening underlies the enhancement of IDE's activity. These findings, together with the adverse effects of anionic membranes in the self-assembly of IDE's amyloidogenic substrates, suggest that the lipid composition of membranes is a key determinant of IDE's ability to balance the levels of its physiologically and pathologically relevant substrates and achieve proteostasis.
Publication Title
ACS Omega
Publication Date
7-19-2022
Volume
7
Issue
28
First Page
24757
Last Page
24765
ISSN
2470-1343
DOI
10.1021/acsomega.2c02747
Repository Citation
Zheng, Qiuchen; Lee, Bethany; Kebede, Micheal T.; Ivancic, Valerie A.; Kemeh, Merc M.; Brito, Henrique Lemos; Spratt, Donald E.; and Lazo, Noel D., "Exchange Broadening Underlies the Enhancement of IDE-Dependent Degradation of Insulin by Anionic Membranes" (2022). Chemistry. 122.
https://commons.clarku.edu/chemistry/122
Cross Post Location
Student Publications
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Copyright Conditions
Zheng, Q., Lee, B., Kebede, M. T., Ivancic, V. A., Kemeh, M. M., Brito, H. L., ... & Lazo, N. D. (2022). Exchange broadening underlies the enhancement of IDE-dependent degradation of insulin by anionic membranes. ACS omega, 7(28), 24757-24765.
