Intrinsically disordered domains are now known to be crucial, functional components of many proteins, especially those involved in cell signalling and regulation of the cell cycle. The presence of disordered regions prevents those proteins being crystallised for structural studies, and so solution of their structures is a major challenge, requiring techniques other than x-ray crystallography. The tumour suppressor p53 is an archetypical example of such a protein, as are its negative regulators MDM2 and MDMX. p53 is inactivated directly by mutation in ~50% of human cancers and its apoptopic pathways impaired in the remainder, often by raised levels of MDM2 and MDMX. We have recently solved the structure of p53 in solution using a combination of state-of-the-art NMR spectroscopy, small-angle-x-ray scattering, other biophysical and structural methods, protein engineering and computation. We now wish to do the same for MDMX and MDM2, and their complexes with p53. We wish to reconstruct the structure of p53 and its complexes in solution in order to understand the relationship between p53s structure and activity and how it is regulated by post-translational modification and interaction with other partner proteins. These studies will provide fundamental information on the control of the cell cycle and aid in the development of novel anti-cancer drugs. We have the necessary preliminary data to ensure that these studies should be successful.