Next Article in Journal
A Qualitative Study Exploring the Impact and Effects Following Hospital Discharge of COVID-19
Next Article in Special Issue
Three-Dimensional Airway Spheroids and Organoids for Cystic Fibrosis Research
Previous Article in Journal
The Effect of High Flow Nasal Cannula Therapy in Exercised-Induced Asthma of Children
Article

Differential Effects of Oleuropein and Hydroxytyrosol on Aggregation and Stability of CFTR NBD1-ΔF508 Domain

1
Department of Biology, Western Carolina University, Cullowhee, NC 28723, USA
2
Pisgah Labs, Pisgah Forest, NC 28768, USA
3
Office of Sponsored Programs, Virginia Tech, Blacksburg, VA 24060, USA
4
Exela Pharma Sciences, Lenoir, NC 28645, USA
5
Department of Biology, Warren Wilson College, Swannanoa, NC 28778, USA
6
Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, CA 92697, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Massimo Conese and Onofrio Laselva
J. Respir. 2021, 1(3), 204-215; https://doi.org/10.3390/jor1030019
Received: 11 May 2021 / Revised: 22 July 2021 / Accepted: 23 July 2021 / Published: 4 August 2021
Cystic Fibrosis (CF) is caused by loss of function mutations in the Cystic Fibrosis transmembrane conductance regulator (CFTR). The folding and assembly of CFTR is inefficient. Deletion of F508 in the first nucleotide binding domain (NBD1-ΔF508) further disrupts protein stability leading to endoplasmic reticulum retention and proteasomal degradation. Stabilization and prevention of NBD1-ΔF508 aggregation is critical to rescuing the folding and function of the entire CFTR channel. We report that the phenolic compounds Oleuropein and Hydroxytryosol reduce aggregation of NBD1-ΔF508. The NBD1-ΔF508 aggregate size was smaller in the presence of Hydroxytryosol as determined by dynamic light scattering. Neither phenolic compound increased the thermal stability of NBD1-ΔF508 as measured by differential scanning fluorimetry. Interestingly, Hydroxytyrosol inhibited the stabilizing effect of the indole compound BIA, a known stabilizer, on NBD1-ΔF508. Molecular docking studies predicted that Oleuropein preferred to bind in the F1-type core ATP-binding subdomain in NBD1. In contrast, Hydroxytyrosol preferred to bind in the α4/α5/α6 helical bundle of the ABCα subdomain of NBD1 next to the putative binding site for BIA. This result suggests that Hydroxytyrosol interferes with BIA binding, thus providing an explanation for the antagonistic effect on NBD1 stability upon incubation with both compounds. To our knowledge, these studies are the first to explore the effects of these two phenolic compounds on the aggregation and stability of NBD1-ΔF508 domain of CFTR. View Full-Text
Keywords: CFTR; dynamic light scattering; NBD1-ΔF508; phenolic compounds CFTR; dynamic light scattering; NBD1-ΔF508; phenolic compounds
Show Figures

Figure 1

MDPI and ACS Style

Robinson, C.S.; Wyderko, J.A.; Vang, Y.; Martin, G.; Youker, R.T. Differential Effects of Oleuropein and Hydroxytyrosol on Aggregation and Stability of CFTR NBD1-ΔF508 Domain. J. Respir. 2021, 1, 204-215. https://doi.org/10.3390/jor1030019

AMA Style

Robinson CS, Wyderko JA, Vang Y, Martin G, Youker RT. Differential Effects of Oleuropein and Hydroxytyrosol on Aggregation and Stability of CFTR NBD1-ΔF508 Domain. Journal of Respiration. 2021; 1(3):204-215. https://doi.org/10.3390/jor1030019

Chicago/Turabian Style

Robinson, Christopher S., Jennifer A. Wyderko, Yeng Vang, Galen Martin, and Robert T. Youker. 2021. "Differential Effects of Oleuropein and Hydroxytyrosol on Aggregation and Stability of CFTR NBD1-ΔF508 Domain" Journal of Respiration 1, no. 3: 204-215. https://doi.org/10.3390/jor1030019

Find Other Styles

Article Access Map by Country/Region

1
Back to TopTop