Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells.
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.
Mesh Terms:
Cell Cycle, Cell Line, Tumor, DNA Damage, Escherichia coli, Gamma Rays, Gene Expression Regulation, Humans, Intrinsically Disordered Proteins, Models, Molecular, Mutation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins c-mdm2, Recombinant Proteins, Signal Transduction, Tumor Suppressor Protein p53
Cell Cycle, Cell Line, Tumor, DNA Damage, Escherichia coli, Gamma Rays, Gene Expression Regulation, Humans, Intrinsically Disordered Proteins, Models, Molecular, Mutation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins c-mdm2, Recombinant Proteins, Signal Transduction, Tumor Suppressor Protein p53
Nat. Chem. Biol.
Date: Dec. 01, 2014
PubMed ID: 25362358
View in: Pubmed Google Scholar
Download Curated Data For This Publication
187202
Switch View:
- Interactions 3