Undesired usage and the robust self-assembly of heterogeneous structures
Undesired usage and the robust self-assembly of heterogeneous structures
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DOI：
10.1038/ncomms7203
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发表时间：
2015-02-01
影响因子：
16.6
通讯作者：
Brenner, Michael P.
中科院分区：
文献类型：
--
作者：
Murugan, Arvind;Zou, James;Brenner, Michael P.
受生物学中的多蛋白质复合体和最近在合成DNA碎片和胶体自组装方面的成功的启发，我们研究了由多种成分组成的结构的自发组装。实现高组装产量的主要挑战是消除不完整或不正确结合的结构。在这里，我们发现，如果成分浓度反映了所需结构的组成(即化学计量比)，则在不同的组装模型中，随着结构尺寸和复杂性的增加，这种不希望看到的结构会迅速降低产量。但这种产量灾难可以通过使用高度非化学计量比的浓度来缓解。我们的研究结果支持“非预期使用”的一般原则--应该选择成分的浓度来说明它们是如何被非预期结构“利用”的，而不仅仅是被期望的结构所使用。这一原理可能会改进合成组装方法，但也会对形成核糖体等生物复合体的蛋白质的表达水平提出新的问题。
Inspired by multiprotein complexes in biology and recent successes in synthetic DNA tile and colloidal self-assembly, we study the spontaneous assembly of structures made of many kinds of components. The major challenge with achieving high assembly yield is eliminating incomplete or incorrectly bound structures. Here, we find that such undesired structures rapidly degrade yield with increasing structural size and complexity in diverse models of assembly, if component concentrations reflect the composition (that is, stoichiometry) of the desired structure. But this yield catastrophe can be mitigated by using highly non-stoichiometric concentrations. Our results support a general principle of 'undesired usage'-concentrations of components should be chosen to account for how they are 'used' by undesired structures and not just by the desired structure. This principle could improve synthetic assembly methods, but also raises new questions about expression levels of proteins that form biological complexes such as the ribosome.