Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain‐of‐function from the perspective of a fine‐tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding‐induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano‐active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.

中文翻译：

---

蛋白质在体内是否发挥功能性作用？

在力的作用下，多域蛋白的折叠和重折叠尚未被公认为是体内蛋白功能的主要机制。在这篇综述中，我们从结构和功能的角度讨论了力载体下多结构域蛋白的固有特性。然后，我们描述了三个主要系统，其中多域蛋白可通过机械展开发挥主要作用：肌肉收缩，细胞机械转导和细菌粘附。我们从微调的量化响应，分子电池，通过重折叠进行的机械功传递，弹性调整，保护和暴露隐含位点的角度分析了每个系统的关键多域蛋白如何产生功能增益结合引起的机械变化。了解机械性展开和重新折叠如何影响功能，对于设计针对肌肉营养不良，癌症，