Gu Chunkai, Zhang Tuo, Lv Chenyan, Liu Yu, Wang Yingjie, Zhao Guanghua
College of Food Science & Nutritional Engineering, China Agricultural University, Key Laboratory of Functional Dairy, Ministry of Education, Beijing 100083, China.
ACS Nano. 2020 Dec 22;14(12):17080-17090. doi: 10.1021/acsnano.0c06670. Epub 2020 Nov 16.
Protein nanocages represent a class of nanovehicles for a variety of applications. However, precise manipulation of self-assembly behavior of these protein nanocages in response to multiple external stimuli for custom-tailored applications remains challenging. Herein, we established a simple but effective strategy for controlling protein nanocage self-assembly that combines a dual property of His motifs (their significantly pH-dependent protonation state and their capacity to coordinate with transition metals) with its high symmetry. With this strategy, we enabled two different ferritin nanocages to disassemble into protein tetramers under neutral solution by introducing His motifs at the 4-fold channel interfaces. Notably, these tetramers are able to self-assemble into ferritin-like protein nanocages in response to multiple external stimuli such as transition metal ions and pH, and , indicative of a reversible self-assembly process. Furthermore, such His-mediated reversible protein self-assembly has been explored for encapsulation of bioactive cargo molecules within these reconstituted protein nanocages with higher loading efficiency under milder conditions as compared to the reported acid denaturation encapsulation method for ferritin.
蛋白质纳米笼是一类可用于多种应用的纳米载体。然而，要精确控制这些蛋白质纳米笼在多种外部刺激下的自组装行为以实现定制应用仍然具有挑战性。在此，我们建立了一种简单而有效的策略来控制蛋白质纳米笼的自组装，该策略将组氨酸基序的双重特性（其显著的pH依赖性质子化状态及其与过渡金属配位的能力）与其高对称性相结合。通过这种策略，我们通过在四重通道界面引入组氨酸基序，使两种不同的铁蛋白纳米笼在中性溶液中分解为蛋白质四聚体。值得注意的是，这些四聚体能够响应多种外部刺激（如过渡金属离子和pH）自组装成铁蛋白样蛋白质纳米笼，这表明这是一个可逆的自组装过程。此外，与报道的用于铁蛋白的酸变性包封方法相比，这种组氨酸介导的可逆蛋白质自组装已被用于在更温和的条件下将生物活性货物分子封装在这些重构的蛋白质纳米笼中，且具有更高的装载效率。
