Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.
The Journal of general physiology
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; Royal, Perrine; Stengel, Karen; Sandoz, Guillaume; and Kohout, Susy C, "Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity." (2018). Cooper Medical School of Rowan University Faculty Scholarship. 12.
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Rayaprolu, Vamseedhar et al. “Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.” The Journal of general physiology vol. 150,5 (2018): 683-696. doi:10.1085/jgp.201812064
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