Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity
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Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P3 or PI(3,4)P2 Our results indicate that dimerization plays a significant role in Ci-VSP function.
Rayaprolu, Vamseedhar, Perrine Royal, Karen Stengel, Guillaume Sandoz, and Susy C. Kohout. "Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity." Journal of General Physiology 150, no. 5 (May 2018): 683-696. DOI:10.1085/jgp.201812064.