9my3
Structure of Xenopus KCNQ1-CaM in GDN
Structural highlights
FunctionKCNQ1_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 PubMedVoltage-gated potassium ion (K(+)) channels perform critical roles in many physiological processes, while gain- or loss-of-function mutations lead to life-threatening pathologies. Here, we establish the high-resolution structure of a pivotal intermediate state of the Kv7.1 (KCNQ1) channel using cryogenic electron microscopy. The 3.53 A resolution structure reveals straightened upper S1 and S2 voltage sensor helices, distancing them from the pore filter helix compared to fully activated channels. The outward translation of the S4 voltage sensor is essentially complete in this intermediate state, and the S4-S6 helices and the S4-S5 linker do not change position significantly between intermediate and activated states. The PIP2 ligand can bind in both states. Movement of S1 and S2 helices towards the filter helix from intermediate to activated states may explain smaller components of KCNQ1 voltage sensor fluorescence, differential Rb(+)/K(+) selectivity, and pharmacological responses to activators and inhibitors. Single channel recordings and the location of long QT mutations suggest the potential physiological and disease importance of the intermediate state. A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.,Kyriakis E, Sastre D, Eldstrom J, Roscioni A, Russo S, Ataei F, Dou Y, Chan M, Molinarolo S, Maragliano L, Van Petegem F, Fedida D Nat Commun. 2025 Oct 3;16(1):8814. doi: 10.1038/s41467-025-64060-3. PMID:41044058[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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