Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells
Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells
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DOI：
10.1038/nchembio.1668
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发表时间：
2014-12-01
影响因子：
14.8
通讯作者：
Daughdrill, Gary W.
中科院分区：
文献类型：
--
作者：
Borcherds, Wade;Theillet, Francois-Xavier;Daughdrill, Gary W.
无序相互作用结构域中的残留结构水平决定了体外结合亲和力，但它们是否在细胞中发挥类似的作用尚不清楚。在这里，我们表明，增加残余p53螺旋导致更强的Mdm 2结合，改变p53动力学，受损的靶基因表达和未能诱导细胞周期停滞后DNA损伤。这些结果证实了残余结构是细胞中信号保真度的重要决定因素。
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.