Calmodulin binds to Drosophila TRP with an unexpected mode
| Autor: | Craig Montell, Weidi Chen, Mingjie Zhang, Ziling Sun, Fei Ye, Sabrina Asteriti, Wei Liu, Jun Wan, Roger C. Hardie, Zijing Chen, Zeyu Shen |
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| Přispěvatelé: | Hardie, Roger [0000-0001-5531-3264], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
calmodulin
visual signal transduction animal structures Calmodulin TRPC4 03 medical and health sciences Transient receptor potential channel Mice Transient Receptor Potential Channels Structural Biology Negative feedback Animals Drosophila Proteins Humans Molecular Biology Drosophila TRP 030304 developmental biology TRPC Cation Channels 0303 health sciences Binding Sites biology Chemistry 030302 biochemistry & molecular biology Visual Signal Transduction Ca(2+)-dependent target binding Drosophila melanogaster HEK293 Cells Mutation biology.protein Molecular mechanism Biophysics Calcium Linker Visual phototransduction Protein Binding |
| Popis: | Drosophila TRP is a calcium-permeable cation channel essential for fly visual signal transduction. During phototransduction, Ca2+ mediates both positive and negative feedback regulation on TRP channel activity, possibly via binding to calmodulin (CaM). However, the molecular mechanism underlying Ca2+ modulated CaM/TRP interaction is poorly understood. Here, we discover an unexpected, Ca2+-dependent binding mode between CaM and TRP. The TRP tail contains two CaM binding sites (CBS1 and CBS2) separated by an ∼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 Ca2+-mediated feedback on the channel activity. Finally, we discover that TRPC4, the closest mammalian paralog of Drosophila TRP, adopts a similar CaM binding mode. |
| Databáze: | OpenAIRE |
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