Disordered Regions of Condensate-promoting Proteins Have Distinct Molecular Signatures Associated with Cellular Function

Abstract

Disordered regions of proteins play crucial roles in cellular functions through diverse mechanisms. Some disordered regions function by promoting the formation of biomolecular condensates through dynamic multivalent interactions. While many have assumed that interactions among these condensate-promoting disordered regions are non-specific, recent studies have shown that distinct sequence compositions and patterning lead to specific condensate compositions associated with cellular function. Despite in-depth characterization of several key examples, the full chemical diversity of condensate-promoting disordered regions has not been surveyed. Here, we define a list of disordered regions of condensate-promoting proteins to survey the relationship between sequence and function. We find that these disordered regions show amino acid biases associated with different cellular functions. These amino acid biases are evolutionarily conserved in the absence of positional sequence conservation. Overall, our analysis highlights the relationship between sequence features and function for condensate-promoting disordered regions. This analysis suggests that molecular signatures encoded within disordered regions could impart functional specificity.

Keywords: biomolecular condensates; intrinsically disordered regions.