Structure- and mechanism-guided design of single fluorescent protein-based biosensors
Structure- and mechanism-guided design of single fluorescent protein-based biosensors
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DOI：
10.1038/s41589-020-00718-x
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发表时间：
2021-02-08
影响因子：
14.8
通讯作者：
Campbell, Robert E.
中科院分区：
文献类型：
--
作者：
Nasu, Yusuke;Shen, Yi;Campbell, Robert E.
强度基因编码生物传感器基于单个荧光蛋白荧光的变构调节，是实现神经活动和其他细胞生化事件成像的强大工具。此类生物传感器的典型例子是GCaMP系列Ca2+生物传感器，该传感器在过去二十年中得到了稳步改进，现已成为神经科学不可或缺的工具。然而，没有其他生物传感器能够达到与 Ca2+ 生物传感器相媲美的性能水平，或者在特定学科内产生革命性影响。在造成这种情况的众多原因中，一个关键因素是生物传感器结构和机制的一般黑盒视图。在此视角下，我们旨在总结有关生物传感器结构和机制的已知知识，并在此基础上提供指导，以加速开发更广泛的生物传感器，其性能可与 GCaMP 系列相媲美。利用有关基因编码荧光生物传感器的结构和机制的广泛知识，本视角提供指导，以帮助和加速越来越广泛的高性能成像工具的开发。
Intensiometric genetically encoded biosensors, based on allosteric modulation of the fluorescence of a single fluorescent protein, are powerful tools for enabling imaging of neural activities and other cellular biochemical events. The archetypical example of such biosensors is the GCaMP series of Ca2+ biosensors, which have been steadily improved over the past two decades and are now indispensable tools for neuroscience. However, no other biosensors have reached levels of performance, or had revolutionary impacts within specific disciplines, comparable to that of the Ca2+ biosensors. Of the many reasons why this has been the case, a critical one has been a general black-box view of biosensor structure and mechanism. With this Perspective, we aim to summarize what is known about biosensor structure and mechanisms and, based on this foundation, provide guidelines to accelerate the development of a broader range of biosensors with performance comparable to that of the GCaMP series.Using extensive knowledge about the structures and mechanisms of genetically encoded fluorescent biosensors, this Perspective provides guidelines to aid and accelerate the development of an increasingly broad range of high-performance imaging tools.