Wyatt Technology's light scattering system has been selected by the MRC Centre for Protein Engineering to investigate the interactions of the p53 tumour suppressor gene with S100 protein.
Wyatt's static Multi-Angle Light Scattering (MALS) systems further cancer research by studying how S100 proteins influence the oligomerisation of p53 following separation by size exclusion chromatography (SEC).
The p53 tumour suppressor gene prevents cancer by regulating the cell cycle, activating DNA repair proteins and initiating apoptosis.
However, when the p53 gene is mutated, it can no longer serve its tumour suppressor role and instead leads to cancer growth.
Research has demonstrated that p53 is mutated in more than 50 per cent of human cancers, with mutations mapping mainly to the DNA-binding core domain.
At its Laboratory for Molecular Biology (LMB), the MRC Centre for Protein Engineering undertakes research in an attempt to provide an understanding of the thermodynamic basis for the interactions of p53 with DNA and other proteins, as well as the effects of mutation on these interactions.
The aim is to develop short peptides able to rescue p53 mutants.
The S100 family is a group of dimeric, calcium-binding proteins, which have been found to be over-expressed in several types of cancer.
S100 proteins bind to the C-terminal region of p53, which encompasses a tetramerisation domain.
Part of the research at the LMB is to investigate how S100 proteins bind to p53 in its different oligomeric states, using monomeric and dimeric p53 mutants.
The p53 variants have a large fraction of intrinsically disordered structure and do not elute according to globular protein standards in SEC.
In response, Wyatt Technology's static MALS has been chosen as the most suitable detection technology to study the complex formation of S100 proteins and p53 by determining the molecular weight of the complexes independently of protein standards.
The studies of the complex formation of p53 and S100 proteins by Wyatt's SEC-MALS instrumentation have helped to understand how S100 proteins influence the oligomerisation of p53.
Based on these results and in-vivo studies, a binding model has been established where S100 proteins can activate tetrameric p53 while inhibiting p53 activity binding to the monomer by shifting the tetramerisation equilibrium.
The analytical capabilities of the MALS technology are detailed in a new application note, entitled 'Protein-Protein Interactions of Tumor Suppressor p53 with S100 Proteins', which is available to download from the company's website.
