Conformational disorder in phosphopeptides: solution studies by CD and NMR techniques

In the last few years intrinsically disordered proteins (IDPs) have received great attention from the scientific community as they participate in several important biological processes and diseases. The intrinsic disorder and flexibility of IDPs grant them a number of advantages with respect to ordered proteins, such as conformational plasticity to bind several targets, a large interaction surface, involvement in high specificity/low affinity interactions, enhanced binding kinetics. It is assumed that post-translational modifications such as phosphorylation can stimulate structural rearrangement in IDPs and facilitate their binding to partners. To better understand at a structural level the multifaceted mechanisms that govern molecular recognition processes involving IDPs, we designed, synthesized by solid phase methods, and structurally characterized unstructured peptides. These molecules contain a putative disordered module, flanked at either the N- or C-terminal ends by a different phosphorylated amino acid (serine or threonine) to mimick the effects of phosphorylation. The absence of an ordered state in the designed peptides was proved experimentally by CD and NMR conformational studies that were carried out under different solution conditions.