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

November 2nd, 2014 by Wade Borcherds

Nature Chemical Biology 10, 1000 (2014). doi:10.1038/nchembio.1668

Authors: Wade Borcherds, Fran├žois-Xavier Theillet, Andrea Katzer, Ana Finzel, Katie M Mishall, Anne T Powell, Hongwei Wu, Wanda Manieri, Christoph Dieterich, Philipp Selenko, Alexander Loewer & Gary W Daughdrill

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.

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells