7cqp | pdb_00007cqp
Complex of TRPC4 and Calmodulin_Nlobe
Structural highlights
FunctionCALM1_MOUSE 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. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (By similarity).[UniProtKB:P0DP23] Publication Abstract from PubMedDrosophila TRP is a calcium-permeable cation channel essential for fly visual signal transduction. During phototransduction, Ca(2+) mediates both positive and negative feedback regulation on TRP channel activity, possibly via binding to calmodulin (CaM). However, the molecular mechanism underlying Ca(2+) modulated CaM/TRP interaction is poorly understood. Here, we discover an unexpected, Ca(2+)-dependent binding mode between CaM and TRP. The TRP tail contains two CaM binding sites (CBS1 and CBS2) separated by an approximately 70-residue linker. CBS1 binds to the CaM N-lobe and CBS2 recognizes the CaM C-lobe. Structural studies reveal the lobe-specific binding of CaM to CBS1&2. Mutations introduced in both CBS1 and CBS2 eliminated CaM binding in full-length TRP, but surprisingly had no effect on the response to light under physiological conditions, suggesting alternative mechanisms governing Ca(2+)-mediated feedback on the channel activity. Finally, we discover that TRPC4, the closest mammalian paralog of Drosophila TRP, adopts a similar CaM binding mode. Calmodulin binds to Drosophila TRP with an unexpected mode.,Chen W, Shen Z, Asteriti S, Chen Z, Ye F, Sun Z, Wan J, Montell C, Hardie RC, Liu W, Zhang M Structure. 2021 Apr 1;29(4):330-344.e4. doi: 10.1016/j.str.2020.11.016. Epub 2020 , Dec 15. PMID:33326749[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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