Tee, Wei-Ven & Guarnera, Enrico & Berezovsky, Igor. (2020). Disorder driven allosteric control of protein activity. Current Research in Structural Biology. 2. 191. 10.1016/j.crstbi.2020.09.001.
Studies of protein allostery increasingly reveal an involvement of the back and forth order-disorder transitions in this mechanism of protein activity regulation. Here, we investigate the allosteric mechanisms mediated by structural disorder using the structure-based statistical mechanical model of allostery (SBSMMA) that we have previously developed. We show that SBSMMA accounts for the energetics and causality of allosteric communication underlying dimerization of the BirA biotin repressor, activation of the sortase A enzyme, and inhibition of the Rac1 GTPase. Using the SBSMMA, we also show that introducing structural order or disorder in various regions of esterases can originate tunable allosteric modulation of the catalytic triad. On the basis of obtained results, we propose that operating with the order-disorder continuum allows one to establish an allosteric control scale for achieving desired modulation of the protein activity.
This work was supported by the core funding provided by the Biomedical Research Council (BMRC) of the Agency for Science, Technology and Research (A∗STAR), Singapore.
This is a version of record published in Current Research in Structural Biology. The final authenticated version is available online at: https://doi.org/10.1016/j.crstbi.2020.09.001