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Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells
Wade Borcherds1, François-Xavier Theillet2, Andrea Katzer3
11] Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA. [2] Center for Drug Discovery and Innovation, University of South Florida, Tampa, Florida, USA.
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.
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