Does protein unfolding play a functional role in vivo ?
Does protein unfolding play a functional role in vivo ?
复制标题
蛋白质解折叠在体内发挥功能作用吗？
DOI：
10.1111/febs.15508
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Popa, Ionel
中科院分区：
文献类型：
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作者：
Sharma, Sabita;Subramani, Smrithika;Popa, Ionel
多结构域蛋白在外力作用下的去折叠和重折叠是蛋白质在体内发挥功能的主要机制。在这篇综述中，我们讨论了力矢量下的多结构域蛋白质的结构和功能的角度来看，固有的属性。然后，我们描述了三个主要的系统，其中多结构域蛋白质可以发挥主要作用，通过机械展开：肌肉收缩，细胞mechanotransduction，和细菌粘附。我们分析了每个系统的关键多结构域蛋白质如何从微调的量化响应，分子电池，通过重折叠传递机械功，弹性调整，保护和暴露隐蔽位点以及结合诱导的机械变化的角度产生功能增益。了解机械展开和重折叠如何影响功能将对设计针对肌肉萎缩症，癌症或新型抗生素等疾病的机械活性药物具有重要意义。
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteinsin 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.