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. 2014 Dec;10(12):1000-2.
doi: 10.1038/nchembio.1668. Epub 2014 Nov 2.

Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells

Wade Borcherds  1 , François-Xavier Theillet  2 , Andrea Katzer  3 , Ana Finzel  3 , Katie M Mishall  1 , Anne T Powell  1 , Hongwei Wu  1 , Wanda Manieri  4 , Christoph Dieterich  5 , Philipp Selenko  2 , Alexander Loewer  3 , Gary W Daughdrill  1
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Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells

Wade Borcherds et al. Nat Chem Biol. 2014 Dec.

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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