Beta Turn Propensity and Polymer Scaling Exponent Identify Intrinsically Disordered Proteins that Phase Separate [article]

Elisia A Paiz, John J Correia, Nicholas C Fitzkee, Loren E Hough, Steven T Whitten
2020 bioRxiv   pre-print
The complex cellular milieu can spontaneously de-mix in a process driven in part by proteins that are intrinsically disordered (ID). We hypothesized that protein self-interactions that determine the polymer scaling exponent, v, of monomeric ID proteins (IDPs), also facilitate de-mixing transitions into phase separated assemblies. We analyzed a protein database containing subsets that are folded, ID, or IDPs identified previously to spontaneously phase separate. We found that the subsets
more » ... the subsets differentiated into distinct protein classes according to sequence-based calculations of v and, surprisingly, the propensity in the sequence for adopting the β-turn. Structure-based simulations find that transient β-turn structures reduce the desolvation penalty of forming a protein-rich phase. By this mechanism, β-turns act as energetically favored nucleation points, which may explain the increased propensity for turns in IDPs that are utilized biologically for phase separation.
doi:10.1101/2020.07.06.189613 fatcat:nsm7ikb5lrf25kfbjokstgrvwq