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UK Center Studying p53-S100 Protein Interaction with Wyatt's MALS Systems


The UK's MRC Centre for Protein Engineering has chosen Wyatt Technology's Multiple-Angle Light Scattering system to study the interaction of the p53 gene with the S100 protein, Wyatt said this week.

Specifically, MRC is using the technology to study how S100 proteins influence the oligomerization of p53.

S100 is a group of dimeric, calcium-binding proteins that have been found to be overexpressed in several cancers. S100 proteins bind to the C-terminal region of p53, which encompasses a tetramerization domain. Among other things, MRC is investigating how S100 binds to p53 in its different oligomeric states using monomeric and dimeric p53 mutants, Wyatt said in a statement.

While wild-type p53 prevents cancer by regulating the cell cycle, when mutated, it instead leads to cancer growth. In more than half of human cancers, p53 is mutated, research has found.

The MRC's Laboratory for Molecular Biology is seeking to understand the thermodynamic basis for the interactions of p53 with DNA and proteins, "as well as the effects of mutation on these interactions," Wyatt said. "The goal is to develop short peptides able to rescue p53 mutants."

The p53 variants have a large fraction of intrinsically disordered structure and do not elute according to globular protein standards in size exclusion chromatography. Wyatt's MALS system, however, was chosen because it can determine the molecular weight of complexes independent of protein standards.

Work already done by MRC researchers with the MALS system has resulted in a binding model where S100 proteins activate tetrameric p53 while inhibiting p53 binding to the monomer by shifting the tetramerization equilibrium, Wyatt said.

Based in Santa Barbara, Calif., Wyatt manufactures and sells instruments for absolute macromolecular characterization.

The Centre for Protein Engineering was set up on 1989 at the University of Cambridge to facilitate the study of protein structure and design. It is funded by the Medical Research Council.

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