AbstractThe 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 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.

operon of Streptococcus pneumoniae regulates metal homeostasis and 1 cellular metabolism during zinc-stress 2 3 11 12 13 14 Running Head: S. pneumoniae metabolism altered by zinc-sensitive operon 15 16 17 Corresponding author: Justin A. Thornton, thornton@biology.msstate.edu 18 19 20 21induced during zinc-limiting conditions. This operon was found to be regulated by a zinc-47 dependent regulator (SP1433) that functions independently of the overarching AdcR regulon. 48We have additionally utilized a 2D-NMR approach to analyze the secreted metabolome and 49 have employed proteomic analysis to identify a role for these systems in the maintenance of 50 cellular metabolism. This study provides new information on how Streptococcus pneumoniae 51 responds and adapts to zinc-limiting conditions. 52 53