Structural determinants of KvLQT1 control by the KCNE family of proteins

KvLQT1 is a Shaker like voltage-gated potassium channel that when complexed with minK (KCNE1) pro duces the slowly activating delayed rectifier I-ks. The emerging family of KCNE1-related peptides includes KCNE1 and KCNE3, bot h of which complex with KvLQT1 to produce functionally distinct currents. N amely I-ks, the slowly activating delayed rectifier current, is produced by KvLQT1/KCNE1, whereas KvLQT1/KCNE3 yields a more rapidly activating curren t with a distinct constitutively active component. We exploited these funct ional differences and the general structural similarities of KCNE1 and KCNE 3 to study which physical regions are critical for control of KvLQT1 by mak ing chimerical constructs of KCNE1 and KCNE3. By using this approach, we ha ve found that a three-amino acid stretch within the transmembrane domain is necessary and sufficient to confer specificity of control of activation ki netics by KCNE1 and KCNE3. Moreover, chimera analysis showed that different regions within the transmembrane domain control deactivation rates. Our re sults help to provide a basis for understanding the mechanism by which KCNE proteins control K+ channel activity.