Calmodulin binds to Drosophila TRP with an unexpected mode.

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. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Weidi Chen, Zeyu Shen, Sabrina Asteriti, Zijing Chen, Fei Ye, Ziling Sun, Jun Wan, Craig Montell, Roger C Hardie, Wei Liu, Mingjie Zhang. Calmodulin binds to Drosophila TRP with an unexpected mode. Structure (London, England : 1993). 2021 Apr 01;29(4):330-344.e4

PMID: 33326749

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