6b8q
From Proteopedia
Crystal Structure of the Mg2+/CaM:Kv7.5 (KCNQ5) AB domain complex
Structural highlights
DiseaseKCNQ5_HUMAN The disease is caused by mutations affecting the gene represented in this entry. FunctionKCNQ5_HUMAN Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. Therefore, it is important in the regulation of neuronal excitability. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current. Insensitive to tetraethylammonium, but inhibited by barium, linopirdine and XE991. Activated by niflumic acid and the anticonvulsant retigabine. As the native M-channel, the potassium channel composed of KCNQ3 and KCNQ5 is also suppressed by activation of the muscarinic acetylcholine receptor CHRM1.[1] [2] [3] Publication Abstract from PubMedKv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT. A Calmodulin C-Lobe Ca(2+)-Dependent Switch Governs Kv7 Channel Function.,Chang A, Abderemane-Ali F, Hura GL, Rossen ND, Gate RE, Minor DL Jr. Neuron. 2018 Feb 21;97(4):836-852.e6. doi: 10.1016/j.neuron.2018.01.035. Epub, 2018 Feb 8. PMID:29429937[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
