Biological evolution has led to precise and dynamic nanostructures that reconfigure in response to pH and other environmental conditions. However, designing micrometre-scale protein nanostructures that are environmentally responsive remains a challenge. Here we describe the de novo design of pH-responsive protein filaments built from subunits containing six or nine buried histidine residues that assemble into micrometre-scale, well-ordered fibres at neutral pH. The cryogenic electron microscopy structure of an optimized design is nearly identical to the computational design model for both the subunit internal geometry and the subunit packing into the fibre. Electron, fluorescent and atomic force microscopy characterization reveal a sharp and reversible transition from assembled to disassembled fibres over 0.3 pH units, and rapid fibre disassembly in less than 1 s following a drop in pH. The midpoint of the transition can be tuned by modulating buried histidine-containing hydrogen bond networks. Computational protein design thus provides a route to creating unbound nanomaterials that rapidly respond to small pH changes.

生物进化产生了精确且动态的纳米结构，可以根据 pH 值和其他环境条件进行重新配置。然而，设计对环境敏感的微米级蛋白质纳米结构仍然是一个挑战。在这里，我们描述了 pH 响应蛋白丝的从头设计，该蛋白丝由含有六或九个埋藏组氨酸残基的亚基构建，这些亚基在中性 pH 下组装成微米级、有序的纤维。优化设计的低温电子显微镜结构与亚基内部几何形状和亚基填充到光纤中的计算设计模型几乎相同。电子、荧光和原子力显微镜表征揭示了超过 0.3 pH 单位从组装纤维到分解纤维的急剧且可逆的转变，以及在 pH 值下降后不到 1 秒的时间内纤维快速分解。转变的中点可以通过调节埋入的含组氨酸的氢键网络来调节。因此，计算蛋白质设计提供了一条创建可快速响应微小 pH 变化的未结合纳米材料的途径。