Electrostatic interactions in molecular recognition of intrinsically disordered proteins.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are abundant in all species. They play critical roles in many cellular processes, including transcription/translation regulation, cell cycle regulation, mRNA processing, scaffolding, apoptosis, and assembly of large protein complexes or membraneless organelles. IDPs/IDRs usually recognize their biological targets via short recognition segments. Although the recognition segments are enriched in hydrophobic residues and IDPs/IDRs rely on hydrophobic contacts to interact with their targets, charged residues are also frequently observed within the recognition segments, particularly in those forming α-helix in the complex structure. By summarizing recent studies, this review aims to present the roles of electrostatic interactions played in the molecular recognition processes of IDPs/IDRs. In particular, we discuss how electrostatic interactions modulate the molecular recognition mechanisms and how charge patterning modulates the functions of IDPs/IDRs. Roles of electrostatic interactions in liquid-liquid phase separation are also discussed.Communicated by Ramaswamy H. Sarma.