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Free keywords:
Cell Cycle/genetics/radiation effects
Cell Line, Tumor
DNA Damage
Escherichia coli/genetics/metabolism
Gamma Rays
Gene Expression Regulation
Humans
Intrinsically Disordered Proteins/*chemistry/genetics/metabolism
Models, Molecular
Mutation
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Proto-Oncogene Proteins c-mdm2/*chemistry/genetics/metabolism
Recombinant Proteins/chemistry/genetics/metabolism
*Signal Transduction
Tumor Suppressor Protein p53/*chemistry/genetics/metabolism
Abstract:
Levels of residual structure in disordered interaction domains determine in vitro binding affinities, but whether they exert similar roles in cells is not known. Here, we show that increasing residual p53 helicity results in stronger Mdm2 binding, altered p53 dynamics, impaired target gene expression and failure to induce cell cycle arrest upon DNA damage. These results establish that residual structure is an important determinant of signaling fidelity in cells.