6b8n
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(New page: ==Crystal Structure of the Ca2+/CaM:Kv7.4 (KCNQ4) AB Domain Complex, 10 uM CaCl2 soak== <StructureSection load='6b8n' size='340' side='right' caption='6b8n, resolution ...)
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Revision as of 06:30, 14 March 2018
proteopedia linkproteopedia linkCrystal Structure of the Ca2+/CaM:Kv7.4 (KCNQ4) AB Domain Complex, 10 uM CaCl2 soak
Structural highlights
Disease[KCNQ4_HUMAN] Defects in KCNQ4 are the cause of deafness autosomal dominant type 2A (DFNA2A) [MIM:600101]. DFNA2A is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.[1] [2] [3] [4] [5] [CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. Function[KCNQ4_HUMAN] Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.[6] [CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[7] [8] [9] [10] 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[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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