LOCATE reveals electrostatic “islands” and “hotspots” are important for a disordered clock protein's interactions to regulate clock robustness

Abstract

Many important biological processes are regulated by the circadian molecular clock, a negative feedback loop comprised of disordered proteins. The lack of a fixed conformation means that identifying interaction regions on core clock proteins is untenable using typical biophysical methods. Since disordered proteins often interact through short linear binding motifs (SLiMs), we decided to take a divide-and-conquer approach leveraging synthetic peptide technology. Our method termed Linear mOtif disCovery using rATional dEsign (LOCATE) takes a disordered protein sequence and divides it into a set of short overlapping peptides that can be synthesized and printed in a microarray format.