Many Light Touches Convey the Message

Our attraction to precision and symmetry in everyday life must be put aside to appreciate how natural selection favors networks governed by weak interactions, multivalency, and proteins described as low complexity (LC) and/or intrinsically disordered (ID). Phosphorylation, ubiquitination, and glycosylation of proteins often act as weak docking sites for multivalent adaptor proteins in the formation of membrane-associated and soluble complexes that mediate information flow in cells. Multiple post-translational modification (PTM) sites together with LC and ID regions in proteins can mediate phase transition from soluble complexes to liquid droplets in the cytoplasm or tethering to the membrane. Although compositionally complex and highly dynamic, these systems display remarkable control of specificity, timing, and switch-like behavior in signaling pathways.

TrendsPTMs control the assembly of signaling complexes, often with fail-safe redundancies in the form of multiple sites.Functional complexes can arise from stochastic binding – an ensemble of transiently bound states – rather than a single terminal conformer.Multivalent and complex systems of proteins, RNA, and/or glycoconjugates can undergo phase transition to form membrane-less liquid droplets, liquid gels, or membrane-associated lattices that serve to transiently rewire biochemical pathways.Asymmetry in the genetic code promotes mutational experimentation with the amino acids that are most likely to yield phenotypic diversity through PTMs. The probable coevolution of ancient PTMs and the genetic code has entrenched this relationship as a key feature of evolvability and advancing complexity.