Title
Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.
Document Type
Article
Version Deposited
Published Version
Publication Date
5-7-2018
Publication Title
The Journal of general physiology
DOI
10.1085/jgp.201812064
Abstract
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.
Recommended Citation
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.
https://rdw.rowan.edu/cmsru_facpub/12
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
Published Citation
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
Comments
psted after 6 month embargo per publisher requirements