蛋白质隐态构象

Invisible Protein State

生物活性蛋白质的结构具有动态特性,存在构象系综,包含常规结构生物学可测定的稳态和常规结构生物学无法测定的隐态构象。隐态构象与稳态构象之间存在着多态平衡,在蛋白质生物学功能上具有重要作用。蛋白质隐态定义起源于蛋白质折叠机制及蛋白质分子动态学研究。在蛋白质构象系综中,蛋白质隐态的含量较少、寿命短及较稳态构象能量高等性质使得隐态难以被捕捉与解析。随着核磁共振波普技术的迅速发展,在实验方法上探索蛋白质动态构象特性逐渐引人瞩目。研究蛋白质隐态构象及蛋白质不同构象之间的相互转变机制,有助于阐明蛋白质分子识别机制,为指导靶向药物设计提供新的理论依据。本文对蛋白质隐态定义进行了溯源,简述了蛋白质隐态的基本性质,探讨了蛋白质隐态对经典分子识别机制"锁匙假说"和"诱导契合假说"发展为"构象选择假说"的贡献。本文进一步简要分析与比较当前结构生物学方法对蛋白质隐态构象分析的优点和缺点,最后对蛋白质隐态研究进行了展望。

Conformation dynamics attributes to the biological functions of active proteins and conformation ensembles.The conformation ensembles include protein stable states(PSS)that can be measured by conventional structural biology approaches and the invisible protein states(IPS)that cannot be measured by conventional structural biology ones.The conformational exchange between IPS and PSS plays an important role in the biological functions of proteins.In this review,we briefly describe the basic properties of IPS and discuss its contribution to the development of the classical molecular recognition mechanism of"key-lock hypothesis"and"induced fit hypothesis"into"conformational selection hypothesis".Furthermore,this review compares the advantages and disadvantages of the current structural biology approaches for investigating the conformational properties of IPS.Because of advanced NMR technology,the exploration of the conformational properties of IPS in experimental manner has become feasible.It is expected that the study of IPS and its function will not only help clarify the molecule recognition mechanism of proteins,but also provide a basis for guiding the design of targeted drugs.