Reprogramming control of an allosteric signaling switch through modular recombination
Reprogramming control of an allosteric signaling switch through modular recombination
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DOI：
10.1126/science.1085945
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发表时间：
2003-09-26
期刊：
影响因子：
56.9
通讯作者：
Lim, WA
中科院分区：
文献类型：
--
作者：
Dueber, JE;Yeh, BJ;Lim, WA
许多真核信号蛋白由简单的模块结合域组成，但它们可以表现出复杂的行为，如变构门控和多输入信号整合，这些特性对于复杂的细胞电路是必不可少的。为了理解这种行为是如何从简单结构域的组合中出现的，我们设计了肌动蛋白调节蛋白N-WASP(神经元Wiskott-Aldrich综合征蛋白)的变体，其中N-WASP的“输出”域与异源的自抑制“输入”域重组。人工合成的开关蛋白具有不同的门控行为，以响应非生理输入。因此，这种类型的模块化框架可以促进细胞信令电路的进化或工程。
Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.