A New Mechanism of Cellular and Tissue Automaticity

Abstract

methods. Here, we developed a rational design method to obtain a peptide that can bind an IDR using only sequence information (Sci. Rep. 2019). We applied the method to the disordered C-terminal disordered domain of a tumor suppressor p53. The designed peptide showed the suppression of binding to DNA and sliding along DNA by p53 based on NMR, MD, and single molecule measurements (Nucleic Acid Res. 2018). Also, we recently found that p53 itself induces liquid-liquid phase separation through multivalent electrostatic interactions between two IDRs. We showed that the designed peptide suppressed the liquidliquid phase separation of p53 by blocking the interaction of the IDRs. Sequence-based design may be useful in targeting IDRs for therapeutic purposes.