Science Topics - 55
KCNQ1 is a voltage-dependent K+ channel expressed in various tissues such as heart and inner ear, and also known as a causal gene for long QT syndrome. As seen in a protein complex of KCNQ1 and KCNE1 underlying IKs current in heart, biophysical properties of KCNQ1 channel can be dramatically regulated by auxiliary KCNE proteins. To understand the regulatory mechanisms of KCNQ1 by KCNE protein family, we tested whether the movement of voltage sensor domain was affected by the presence of KCNE proteins or not. We introduced several cysteine substitutions on S4 segment, which plays a major role on the voltage sensing, one at a time. We then applied cysteine modifying MTS reagent and examined how the modification rate was affected by the presence of KCNE1 or KCNE3. We found that the “down state” of the voltage sensor was stabilized in the presence of KCNE1 while the “up state” was stabilized in the presence of KCNE3 (Figure). Our results suggest that the voltage sensor is involved in the modulation of KCNQ1 by KCNE family.
(Nakajo & Kubo, J. Gen. Physiol., 130: 269-281, 2007)
KCNE1 (blue) stabilizes the voltage sensor in the “down state” (left). On the other hand, KCNE3 stabilizes the voltage sensor in the “up state” (right).
*Department of Biophysics and Neurobiology, National Institute for Physiological Sciences