Phosphorylation refines the control of complex formation in IDPs.

Abstract

Dynamic and multivalent interactions are hallmarks of intrinsically disordered proteins (IDPs) acting within complex cellular regulatory pathways. Thanks to their astonishing molecular plasticity, IDPs often interact with numerous binding partners. While the interaction networks are expected to be highly regulated, disentangling the underlying regulatory mechanisms remains challenging. The nuclear coactivator binding domain (NCBD) is a known transcriptional hub in regulatory networks. At equilibrium, two conformations of NCBD exist due to the cis/trans isomerization of a single proline residue: an effect previously shown to expand the tunability of complex formation with the activator for thyroid hormone (ACTR) by orders of magnitude. Interestingly, proline residues are often located, as in the case of NCBD, within phosphorylation motifs.