KCNE4, a transmembrane protein, is an accessory subunit belonging to the KCNE family. It functions as a modulator of voltage-gated potassium (Kv) channels such as Kv7.1 (KCNQ1). KCNE4 is unique in the KCNE family as it is known to inhibit Kv current. Incorrect modulation of current through these channels has been linked to several diseases including long QT syndrome, allergic rhinitis, and acute lymphoblastic leukemia. Understanding the dynamics of KCNE4, specifically in disease conditions, will increase our knowledge of the etiology of these diseases, and decrease future drug research bottlenecks. Cholesterol has been implicated in several diseases, including heart disease. It is known to decrease membrane fluidity and increase organization between membrane lipids. Cholesterol has also been shown to modify the function of Kv channels such as Kv7.1. Understanding how cholesterol affects the dynamics of KCNE4 in the membrane would further our understanding of the implicated diseases. To collect dynamic data on membrane proteins, liposomes are often used as a membrane mimetic. Previous studies have used liposomes with 3:1 POPC:POPG; however, a new model will be investigated using 3:1 POPC:POPG with the addition of 15% cholesterol. Continuous wave–electron paramagnetic resonance (CW-EPR) spectroscopy in combination with line-shape analysis reveals site-specific information on the structure and dynamics. In this study, the CW-EPR spectra of the cholesterol-containing liposomes will be gathered and compared to the CW-EPR spectra of liposomes without cholesterol to divulge how the dynamics of regions of KCNE4 are affected by cholesterol.
Author(s): Elizabeth Travis, Alison Bates, Gary A. Lorigan
Advisor(s): Gary Lorigan, Department of Chemistry and Biochemistry
Alison Bates, Department of Chemistry and Biochemistry
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