Department of Materials Science and Engineering, University of California Berkeley, Berkeley, CA, USA.
Department of Chemistry, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Xiamen University, Xiamen, China.
Nature. 2020 Jan;577(7789):216-220. doi: 10.1038/s41586-019-1881-0. Epub 2020 Jan 8.
Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels, both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks. However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs) can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.
精确的蛋白质测序和折叠被认为可以产生天然通道的结构和化学多样性，这两者对于合成具有与天然系统相当的质子传输性能都是至关重要的。已经使用肽、DNA、碳纳米管、序列定义的聚合物和有机框架制造了具有几何定义的通道。然而，这些通道中没有一个能与天然通道的性能相媲美。在这里，我们表明，没有形成原子结构的通道，基于四个单体的随机杂聚物 (RHP) 可以模拟膜蛋白，并在类似天然质子通道的速率下表现出对脂质双层的选择性质子传输。在 RHP 中对单体分布进行统计控制会导致疏水性的分段异质性，这有助于将单个 RHP 插入脂质双层中。它还导致包含极性单体的跨双层片段，这些单体促进了质子传输的氢键链的形成。我们的研究表明，在 RHP 链之间的统计相似性所带来的适应性以及单体化学多样性所提供的模块性对于在异质系统中实现均匀行为非常重要。我们的结果还验证了统计随机性作为一种在可预测的方式下在单聚合物链水平上实现类似蛋白质行为的探索性方法的重要性。
