5vms | pdb_00005vms
CryoEM structure of Xenopus KCNQ1 channel
Structural highlights
Function[KCNQ1_XENLA] Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity). Associates with KCNE beta subunits that modulates current kinetics (By similarity). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (By similarity). When associated with KCNE4, inhibits voltage-gated potassium channel activity (By similarity). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (By similarity).[UniProtKB:P51787][UniProtKB:P97414][UniProtKB:Q9Z0N7] Publication Abstract from PubMedKCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (IKs) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP2-free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP2. CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP2, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.,Sun J, MacKinnon R Cell. 2017 Jun 1;169(6):1042-1050.e9. doi: 10.1016/j.cell.2017.05.019. PMID:28575668[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||
