Uversky Vladimir N
Institute for Intrinsically Disordered Protein Research, The Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Biomed Biotechnol. 2010;2010:568068. doi: 10.1155/2010/568068.
Contrarily to the general believe, many biologically active proteins lack stable tertiary and/or secondary structure under physiological conditions in vitro. These intrinsically disordered proteins (IDPs) are highly abundant in nature and many of them are associated with various human diseases. The functional repertoire of IDPs complements the functions of ordered proteins. Since IDPs constitute a significant portion of any given proteome, they can be combined in an unfoldome; which is a portion of the proteome including all IDPs (also known as natively unfolded proteins, therefore, unfoldome), and describing their functions, structures, interactions, evolution, and so forth. Amino acid sequence and compositions of IDPs are very different from those of ordered proteins, making possible reliable identification of IDPs at the proteome level by various computational means. Furthermore, IDPs possess a number of unique structural properties and are characterized by a peculiar conformational behavior, including their high stability against low pH and high temperature and their structural indifference toward the unfolding by strong denaturants. These peculiarities were shown to be useful for elaboration of the experimental techniques for the large-scale identification of IDPs in various organisms. Some of the computational and experimental tools for the unfoldome discovery are discussed in this review.
与普遍看法相反，许多生物活性蛋白在体外生理条件下缺乏稳定的三级和/或二级结构。这些内在无序蛋白（IDP）在自然界中高度丰富，其中许多与各种人类疾病有关。IDP的功能库补充了有序蛋白的功能。由于IDP构成了任何给定蛋白质组的很大一部分，它们可以组合成一个展开组；展开组是蛋白质组的一部分，包括所有IDP（也称为天然未折叠蛋白，因此称为展开组），并描述它们的功能、结构、相互作用、进化等。IDP的氨基酸序列和组成与有序蛋白非常不同，这使得通过各种计算方法在蛋白质组水平上可靠地鉴定IDP成为可能。此外，IDP具有许多独特的结构特性，并具有特殊的构象行为，包括它们对低pH和高温的高稳定性以及它们对强变性剂展开的结构不敏感性。这些特性已被证明有助于开发用于大规模鉴定各种生物体中IDP的实验技术。本文综述了一些用于展开组发现的计算和实验工具。
