Semibiological molecular machine with an implemented "AND" logic gate for regulation of protein folding

Semibiological molecular machine with an implemented "AND" logic gate for regulation of protein folding
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DOI:
10.1021/ja057604t
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发表时间:
2006-03-22
影响因子:
15
通讯作者:
Aida, T
Aida, T
中科院分区:
化学1区
文献类型:
--
作者:
Muramatsu, S;Kinbara, K;Aida, T

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研制了一种具有"与“逻辑门的半生物分子机器,它能够响应于ATIP和光作为输入刺激来控制蛋白质的折叠过程。分子设计利用基因工程伴侣GroEL轴承,在其圆柱形腔的两个入口部分,半胱氨酸残基,其被功能化的偶氮苯衍生物,以构建光响应机械门(偶氮GroEL)。这种工程伴侣蛋白捕获变性的绿色荧光蛋白(GFP(denat)),并阻止其重折叠。然而,当宿主azo-GroEL同时检测到ATP(输入刺激1)和UV光(输入刺激2)时,它迅速释放GFP(denat)以允许其重折叠。相比之下,接收输入刺激1或2导致GFP denat仅非常缓慢或没有实质性的重折叠。在机械驱动的生物分子系统中实现这种“与”逻辑门机制是设计安全药物递送系统的重要一步。
A semibiological molecular machine with an implemented '' AND '' logic gate was developed, which was capable of controlling the folding process of proteins in response to ATIP and light as input stimuli. The molecular design made use of a genetically engineered chaperonin GroEL bearing, at both entrance parts of its cylindrical cavity, cysteine residues, which were functionalized by an azobenzene derivative to construct photoresponsive mechanical gates (azo-GroEL). This engineered chaperonin trapped denatured green fluorescent protein (GFP(denat)) and prohibited its refolding. However, when hosting azo-GroEL detected ATP (input stimulus 1) and UV light (input stimulus 2) at the same time, it quickly released GFP(denat) to allow its refolding. In contrast, reception of either input stimulus 1 or 2 resulted in only very slow or no substantial refolding of GFPdenat. Implementation of such '' AND '' logic gate mechanisms in mechanically driven biomolecular systems is an important step toward the design of secured drug delivery systems.