Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch.
Synthetic design of farnesyl-electrostatic peptides for development of a protein kinase A membrane translocation switch.
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DOI：
10.1038/s41598-021-95840-8
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发表时间：
2021-08-12
影响因子：
4.6
通讯作者：
Inoue T
中科院分区：
文献类型：
--
作者：
Kim AK;Wu HD;Inoue T
响应细胞中生化刺激的分子开关已被证明是开发分子传感器和致动器的基础，可用于解决重要的生物学问题。不幸的是，开发分子开关仍然很困难，因为它需要构建在单个分子中的传感和致动机制的精心协调。在这里，我们合理地设计了一个分子开关，改变其亚细胞定位，以响应预期的刺激，如蛋白激酶A（PKA）的激活剂。通过串联排列Kemptide的序列，我们设计了一种法尼基化的肽，其定位可以在PKA磷酸化后显著改变。在测试了不同化合价的Kemptide以及调节连接它们的接头序列后，我们鉴定了一种有效的肽开关，其以PKA活性依赖性方式在质膜和内部内膜之间表现出动态易位。由于模块化设计和小尺寸，我们的PKA开关可以在未来的研究中作为可视化和干扰信号转导通路的平台，以及在细胞中进行合成操作的多功能实用程序。
Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires elaborate coordination of sensing and actuation mechanisms built into a single molecule. Here, we rationally designed a molecular switch that changes its subcellular localization in response to an intended stimulus such as an activator of protein kinase A (PKA). By arranging the sequence for Kemptide in tandem, we designed a farnesylated peptide whose localization can dramatically change upon phosphorylation by PKA. After testing a different valence number of Kemptide as well as modulating the linker sequence connecting them, we identified an efficient peptide switch that exhibited dynamic translocation between plasma membranes and internal endomembranes in a PKA activity dependent manner. Due to the modular design and small size, our PKA switch can have versatile utility in future studies as a platform for visualizing and perturbing signal transduction pathways, as well as for performing synthetic operations in cells.
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影响因子：
64.5
作者：
Regot S;Hughey JJ;Bajar BT;Carrasco S;Covert MW
通讯作者：
Covert MW
DOI：
10.1038/nrm3255
发表时间：
2011-12-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Gomez, Guillermo A.;Daniotti, Jose L.
通讯作者：
Daniotti, Jose L.
影响因子：
4.6
作者：
Kim, Allen K.;Wu, Helen D.;Inoue, Takanari
通讯作者：
Inoue, Takanari
影响因子：
2.9
作者：
Roy, MO;Leventis, R;Silvius, JR
通讯作者：
Silvius, JR