Phosphorylation Modulates Conformational Bias of a Disordered Peptide

Abstract

Disordered proteins, proteins lacking a stable three-dimensional structure, are often enriched in a broadly conserved sequence composition and patterning that imbues them with residual conformational bias toward the polyproline-II (PII) conformation. Since post-translational modification often effects biological function, we ask how phosphorylation impacts PII bias and overall geometry of a short, phosphorylatable peptide. We developed a method to use time-correlated single-photon counting data to measure Forster Resonance Energy Transfer (FRET), then subsequently calculate polymer properties of the peptide. We explore the impact of phosphorylation on effective persistence length and end-to-end distance, and compare the results of our experiments to behaviors modeled by a hard-sphere collision simulation.