Expanding the proteome: disordered and alternatively folded proteins.
Expanding the proteome: disordered and alternatively folded proteins.
复制标题
DOI：
10.1017/s0033583511000060
复制
发表时间：
2011-11
影响因子：
6.1
通讯作者：
Dyson, H. Jane
中科院分区：
文献类型：
--
作者：
Dyson, H. Jane
蛋白质为生命提供了许多支架，并进行各种必要的催化反应。这些特征性的功能使我们假定蛋白质只有在结构良好和正确折叠时才具有一般功能。当我们开始探索人类和其他基因组中可能固有的蛋白质序列时，两个明显的事实证明了这一假设：首先，人类基因组中的表观开放阅读框的数量明显小于似乎为高等生物体中所有不同蛋白质编码所必需的数量，第二，由基因组编码的蛋白质序列的很大一部分不能形成稳定的三维结构。显然，基因组必须包括编码多种不同形式的蛋白质，其中一些蛋白质在其功能状态下可能部分或完全无序或不完全结构化。在认识到这种可能性的同时，实验研究也开始发现一些重要的蛋白质分子和结构域的例子，它们在溶液中不完全结构化或完全无序，但仍然保持完美的功能。在随后的几年里，我们看到了实验和基因组注释研究的爆炸式增长，这些研究描绘了内在疾病现象的程度，并探索了其广泛发生的可能生物学原理。对“为什么一个特定的域需要非结构化？”这篇评论提供了一个调查最近在这一领域的新方向，并包括一个评价的作用，不仅是内在无序的蛋白质，但部分结构和高度动态的成员的无序秩序连续。
Proteins provide much of the scaffolding for life, as well as undertaking a variety of essential catalytic reactions. These characteristic functions have led us to presuppose that proteins are in general functional only when well-structured and correctly folded. As we begin to explore the repertoire of possible protein sequences inherent in the human and other genomes, two stark facts that belie this supposition become clear: firstly, the number of apparent open reading frames in the human genome is significantly smaller than appears to be necessary to code for all of the diverse proteins in higher organisms, and secondly that a significant proportion of the protein sequences that would be coded by the genome would not be expected to form stable three-dimensional structures. Clearly the genome must include coding for a multitude of alternative forms of proteins, some of which may be partly or fully disordered or incompletely structured in their functional states. At the same time as this likelihood was recognized, experimental studies also began to uncover examples of important protein molecules and domains that were incompletely structured or completely disordered in solution, yet remained perfectly functional. In the ensuing years, we have seen an explosion of experimental and genome-annotation studies that have mapped the extent of the intrinsic disorder phenomenon and explored the possible biological rationales for its widespread occurrence. Answers to the question “why would a particular domain need to be unstructured?” are as varied as the systems where such domains are found. This review provides a survey of recent new directions in this field, and includes an evaluation of the role not only of intrinsically disordered proteins but of partially structured and highly dynamic members of the disorder-order continuum.