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.
Keywords: Intrinsically disordered proteins; binding mechanism; electrostatic interaction; fuzzy interaction; molecular recognition.