Protein Nanotube Selectively Cleavable with DNA: Supramolecular Polymerization of "DNA-Appended Molecular Chaperones"
Protein Nanotube Selectively Cleavable with DNA: Supramolecular Polymerization of "DNA-Appended Molecular Chaperones"
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DOI：
10.1021/jacs.7b09892
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发表时间：
2018-01-10
影响因子：
15
通讯作者：
Aida, Takuzo
中科院分区：
文献类型：
--
作者：
Kashiwagi, Daiki;Sim, Seunghyun;Aida, Takuzo
在这里，我们报告的分子伴侣GroEL进行，在其顶端域，多个DNA链（理想情况下，共28个DNA链）与定义的寡核苷酸（nt）序列。该设计策略允许制备携带10-nt DNA链的GroEL（10a）和GroEL（10 b），所述10-nt DNA链的10a和10 b在其顶端结构域分别具有互补序列。这些GroEL的一维共组装可能形成具有异常热力学稳定性的蛋白质纳米管NT 10a/10 b，这是由于共组装的异常大的多价性。同样地，即使当顶部结构域DNA链（15 c和10 d）彼此部分互补时，也获得了热稳定的纳米管NT 15 c/10 d。然而，与NT 10a/10 b形成鲜明对比的是，当与DNA 15 d一起孵育时，NT 15 c/10 d迅速且完全解离，因为15 d通过置换10 d的DNA链而优先与NT 15 c/10 d中的15 c的DNA链杂交，以提供GroEL（15 c/15 d）和GroEL（10 d）的混合物。即使在NT 10 c/10 d的存在下，15 d也选择性地切割NT 15 c/10 d，表明NT用于靶向递送的潜在效用。
Here, we report molecular chaperone GroELs that carry, at their apical domains, multiple DNA strands (ideally 28 DNA strands in total) with defined oligonucleotide (nt) sequences. This design strategy allows for the preparation of GroEL(10a) and GroEL(10b) carrying 10-nt DNA strands of 10a and 10b with complementary sequences, respectively, at their apical domains. One-dimensional coassembly of these GroELs is possible to form protein nanotube NT10a/10b with an anomalous thermodynamic stability due to the exceptionally large multivalency for the coassembly. Likewise, comparably stable nanotube NT15c/10d was obtained even when the apical-domain DNA strands (15c and 10d) were partially complementary to one another. Nevertheless, in sharp contrast with NT10a/10b, NT15c/10d, when incubated with DNA 15d, dissociates rapidly and completely because 15d preferentially hybridizes with the DNA strands of 15c in NT15c/10d by displacing those of 10d, to afford a mixture of GroEL(15c/15d), and GroEL(10d). Even in the presence of NT10c/10d, 15d cleaved off NT15c/10d selectively, indicating the potential utility of NTs for targeted delivery.