摘要
循环排列(circular permutation,CP)是自然界中蛋白质进化中产生的一种氨基酸序列重排现象。重排后的某些突变体仍具有类似该野生型蛋白质的天然构象和活性。生物传感器由分子识别单元和信号报告单元2部分组成,其分子识别单元通过分子间相互作用,将生物体内的配体、离子浓度变化等微观过程转变成信号报告单元的可量化的可视化信号,从而实现生物学信号感知与检测。目前,蛋白质循环排列被广泛应用到生物传感器的设计中,成为近年来发展最为迅速的生物探针设计方法,已应用于生物分子的特异性识别和生命活动的实时监测,为病理研究、疾病预防和诊断提供了重要的手段。如何运用蛋白质循环排列,开发出新型可靠的生物传感器,是当前生物传感器设计中面临的1个重要科学问题。为此,本文总结并论述了以下3点工作。首先,本文简述了循环排列的发展历史,总结了循环排列的2种形成机制,通过实例详细阐述了循环排列对蛋白质结构的影响。其次,针对循环排列生物传感器的设计,本文主要以循环排列荧光蛋白(circular permutation fluorescent protein,cpFP)为例,总结了分子识别单元和信号报告单元两方面的设计策略,并汇总了循环排列蛋白质相关数据库。最后,本文总结了循环排列蛋白生物传感器的最新研究进展,展望了循环排列未来的发展方向,分析了目前循环排列生物传感器开发过程中存在的问题,以期为新型生物传感器的开发提供借鉴。
Circular permutation is a phenomenon of amino acid sequence rearrangement that occurs in natureduring protein evolution.After rearrangement,some mutants still have the natural conformation and activity similar to those of the wild-type protein.The biosensor is composed of a molecular recognition unit and a signal reporting unit.Via the interaction between molecules,the molecular recognition unit converts microscopic processes such as ligands and ion concentration changes in organisms into visual signals in the signal reporting unit to realize biological signal perception and detection.At present,protein circular permutation has been widely used in the design of biosensors,and has become the most rapidly developing biological probe design method in recent years.It has been applied to the specific recognition of biological molecules and real-time monitoring of vital activities,providing an important means for pathological research,disease prevention and diagnosis.How to use protein circular permutation to develop new and reliable biosensors is an important scientific question in the design of biosensors.In this review,we cover three important aspects.Firstly,we summarize the development history of circular permutation,including the two mechanisms of circular permutation and examples of the effects of circular permutation on the protein structure.Secondly,in view of the circular array biosensor design,we use circular permutation fluorescent protein(cpFP)as an illustration to summarize the design strategy for the molecular recognition element and the signal report unit,and sum up the circular permutation proteins database.Finally,we cover the circular permutation protein biosensor,envisionthe future development of circular permutation protein biosensors,and analyze the challenges that exist in the development process and the possible solutions,so as to provide a reference for the development of new biological sensors.
作者
邢一莹
秦晓红
米立志
XING Yi-Ying;QIN Xiao-Hong;MI Li-Zhi(Structural and Molecular Biology,School of Life Sciences,Tianjin University,Tianjin 300072,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2023年第12期1673-1684,共12页
Chinese Journal of Biochemistry and Molecular Biology
关键词
循环排列
循环排列荧光蛋白
生物传感器
circular permutation(CP)
circularly permuted fluorescent protein(cpfp)
biosensors