Engineering extrinsic disorder to control protein activity in living cells.
Engineering extrinsic disorder to control protein activity in living cells.
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DOI：
10.1126/science.aah3404
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发表时间：
2016-12-16
期刊：
影响因子：
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通讯作者：
Hahn KM
中科院分区：
文献类型：
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作者：
Dagliyan O;Tarnawski M;Chu PH;Shirvanyants D;Schlichting I;Dokholyan NV;Hahn KM
蛋白质的光遗传学和化学遗传学控制揭示了信号动力学的其他方面。在这里，我们使用光或配体敏感域来调节不同蛋白质的结构紊乱，从而产生强大的变构开关。感觉域被插入到非保守的，表面暴露的环，是紧密的，并确定计算为变构耦合到活性位点。引入运动信号蛋白（激酶，GTP酶，鸟嘌呤交换因子）的变构开关控制与自然活性和非活性状态非常相似的构象之间的转换，并调节活细胞的形态动力学。我们的研究结果说明了一个广泛适用的方法来设计生理蛋白开关。
Optogenetic and chemogenetic control of proteins has revealed otherwise inaccessible facets of signaling dynamics. Here we use light or ligand-sensitive domains to modulate the structural disorder of diverse proteins, thereby generating robust allosteric switches. Sensory domains were inserted into non-conserved, surface exposed loops that were tight and identified computationally as allosterically coupled to active sites. Allosteric switches introduced into motility signaling proteins (kinases, GTPases, guanine exchange factors) controlled conversion between conformations closely resembling natural active and inactive states, and modulated the morphodynamics of living cells. Our results illustrate a broadly applicable approach to design physiological protein switches.