Role of charges in a dynamic disordered complex between an IDP and a folded domain.

Abstract

Protein complexes involving intrinsically disordered proteins (IDPs) cover a continuum from IDPs that fully fold upon binding to IDPs that remain fully disordered in the complex. Here we demonstrate a case of charge-driven interactions of a folded domain with an oppositely charged IDP that remains completely disordered in the complex. Using the negatively charged and fully disordered prothymosin α and the positively charged and folded globular domain of histone H1.0, we show that they form a low-micromolar-affinity complex without fixed relative orientations or persistent contacts between specific residues. Using 25 charge variants of the globular domain, we find that the binding affinity can be modulated both by net charge and charge clustering on the folded domain, indicating some selectivity in highly charged complexes. Our results highlight that a folded protein can provide a charged surface onto which an oppositely charged IDP can bind while retaining disorder. We expect that more such complexes exist.