BPS2026 – The interaction dynamics of highly charged disordered proteins

Highly charged intrinsically disordered proteins (IDPs) play an important role in intracellular interactions, particularly within the nucleus. However, the molecular mechanisms of their interactions often differ from classic textbook notions of biomolecular binding for folded proteins. The combination of single-molecule spectroscopy with molecular simulations and other complementary biophysical techniques has provided an increasingly detailed understanding of these interaction mechanisms. Key insights include the formation of highly disordered complexes, which enable rapid association via fly-casting and rapid dissociation of high-affinity complexes via competitive substitution via ternary complexes. The interactions of charged IDPs with nucleic acids can influence RNA structure and facilitate target search on DNA. Furthermore, in phase separation by complex coacervation, charge interactions enable the formation of highly dynamic biomolecular condensates whose mesoscopic properties can be quantitatively related to the dynamics at the molecular scale.