Uversky Vladimir N, Dunker A Keith
Institute for Intrinsically Disordered Protein Research, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Biochim Biophys Acta. 2010 Jun;1804(6):1231-64. doi: 10.1016/j.bbapap.2010.01.017. Epub 2010 Feb 1.
This review describes the family of intrinsically disordered proteins, members of which fail to form rigid 3-D structures under physiological conditions, either along their entire lengths or only in localized regions. Instead, these intriguing proteins/regions exist as dynamic ensembles within which atom positions and backbone Ramachandran angles exhibit extreme temporal fluctuations without specific equilibrium values. Many of these intrinsically disordered proteins are known to carry out important biological functions which, in fact, depend on the absence of a specific 3-D structure. The existence of such proteins does not fit the prevailing structure-function paradigm, which states that a unique 3-D structure is a prerequisite to function. Thus, the protein structure-function paradigm has to be expanded to include intrinsically disordered proteins and alternative relationships among protein sequence, structure, and function. This shift in the paradigm represents a major breakthrough for biochemistry, biophysics and molecular biology, as it opens new levels of understanding with regard to the complex life of proteins. This review will try to answer the following questions: how were intrinsically disordered proteins discovered? Why don't these proteins fold? What is so special about intrinsic disorder? What are the functional advantages of disordered proteins/regions? What is the functional repertoire of these proteins? What are the relationships between intrinsically disordered proteins and human diseases?
本综述描述了内在无序蛋白质家族，其成员在生理条件下，要么整条链，要么仅在局部区域无法形成刚性的三维结构。相反，这些引人关注的蛋白质/区域以动态集合体的形式存在，其中原子位置和主链拉氏角呈现出极大的时间波动，没有特定的平衡值。已知许多这类内在无序蛋白质执行着重要的生物学功能，而这些功能实际上依赖于缺乏特定的三维结构。这类蛋白质的存在不符合普遍的结构-功能范式，该范式认为独特的三维结构是功能的先决条件。因此，蛋白质结构-功能范式必须扩展，以纳入内在无序蛋白质以及蛋白质序列、结构和功能之间的其他关系。这种范式的转变代表了生物化学、生物物理学和分子生物学的一项重大突破，因为它开启了对蛋白质复杂生命的新理解层面。本综述将尝试回答以下问题：内在无序蛋白质是如何被发现的？为什么这些蛋白质不折叠？内在无序有什么特别之处？无序蛋白质/区域的功能优势是什么？这些蛋白质的功能范围是什么？内在无序蛋白质与人类疾病之间有什么关系？
