A three-amino acid stretch within the transmembrane domain of KCNE proteins is necessary and sufficient to confer specificity of control of KvLQT1 activation kinetics.
A specific three-amino acid stretch in the transmembrane domain of KCNE proteins determines the activation kinetics of the KvLQT1 potassium channel, providing insight into the molecular basis of I(ks) current regulation.
KvLQT1 is a Shaker-like voltage-gated potassium channel that when complexed with minK (KCNE1) produces the slowly activating delayed rectifier I(ks). The emerging family of KCNE1-related peptides includes KCNE1 and KCNE3, both of which complex with KvLQT1 to produce functionally distinct currents. Namely I(ks), the slowly activating delayed rectifier current, is produced by KvLQT1/KCNE1, whereas KvLQT1/KCNE3 yields a more rapidly activating current with a distinct constitutively active component. We exploited these functional differences and the general structural similarities of KCNE1 and KCNE3 to study which physical regions are critical for control of KvLQT1 by making chimerical constructs of KCNE1 and KCNE3. By using this approach, we have found that a three-amino acid stretch within the transmembrane domain is necessary and sufficient to confer specificity of control of activation kinetics by KCNE1 and KCNE3. Moreover, chimera analysis showed that different regions within the transmembrane domain control deactivation rates. Our results help to provide a basis for understanding the mechanism by which KCNE proteins control K(+) channel activity.
Melman et al. (2001) studied this question. Chimerical constructs of KCNE1 and KCNE3 was evaluated on Control of activation kinetics and deactivation rates of KvLQT1. A three-amino acid stretch within the transmembrane domain of KCNE proteins is necessary and sufficient to confer specificity of control of KvLQT1 activation kinetics.