Intrinsically disordered protein
Intrinsically disordered protein
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DOI：
10.1016/s1093-3263(00)00138-8
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发表时间：
2001-01-01
影响因子：
2.9
通讯作者：
Obradovic, Z
中科院分区：
文献类型：
--
作者：
Dunker, AK;Lawson, JD;Obradovic, Z
蛋白质可以以Trinity位一体的结构存在：有序状态，熔融小球和无规卷曲。适合;下面的例子表明，天然蛋白质结构可以对应于三种状态中的任何一种（不仅仅是有序状态），并且蛋白质功能可以由三种状态中的任何一种及其转换产生。(1)在一个可能模仿感染的过程中，fd噬菌体从有序的熔融球状状态转变为无序的熔融球状状态。(2)核小体超乙酰化对DNA复制和转录至关重要;这种化学修饰大大增加了核小体核心颗粒的净负电荷。我们建议，增加的电荷不平衡促进其转换到一个刚性小得多的形式。(3)胆固醇蛋白含有艺术有序结构域，也是一个天然的熔融球状区域。熔化的球状结构域可能作为蛋白质去污剂用于细胞重塑和去除凋亡碎片。(4)在一个关键的信号事件中，钙调磷酸酶中的螺旋被钙调蛋白结合并包围，从而开启钙调磷酸酶的丝氨酸/苏氨酸磷酸酶活性。将钙调磷酸酶螺旋定位在无序区域内对于使钙调蛋白在结合时围绕其靶是必不可少的。(5)钙螯合蛋白通过结合大约50个离子/分子来调节肌浆网中的钙水平。在羧基末端的无序聚阴离子尾部结合许多这些钙离子，可能没有采用独特的结构。除了这些例子之外，我们还将讨论16种具有天然紊乱的蛋白质。这些无序区域包括分子识别结构域、蛋白质折叠抑制剂、柔性接头、熵弹簧、熵钟和熵刚毛。受这些内在障碍的例子的启发，我们正在研究它们之间的关系。氨基酸序列和有序/无序;并且根据该信息，Lye从氨基酸序列预测内在有序/无序。序列-结构关系表明无序是一种编码属性？，最近对29个基因组的预测表明，来自真核生物的蛋白质明显比来自细菌或古细菌的蛋白质具有更多的内在无序，典型地> 30%的真核生物蛋白质具有长度大于或等于50个连续残基的无序区域。(C)2001年，Elsevier Science Inc.
Proteins can exist in, a trinity of structures: the ordered state, the molten globule, and the random coil. The fit;e following examples suggest that native protein structure can correspond to any of the thr-ee states (not just the order-ed state) and that protein function can arise from any of the three states and their transitions. (1) In a process that likely mimics infection, fd phage converts from the ordered into the disordered molten globular state. (2) Nucleosome hyperacetylation is crucial to DNA replication and transcription; this chemical modification greatly increases the net negative charge of the nucleosome core particle. We propose that the increased charge imbalance promotes its conversion to a much less rigid form. (3) Clusterin contains art ordered domain and also a native molten globular region. The molten globular domain likely functions as a proteinaceous detergent for cell remodeling and removal of apoptotic debris. (4) lit a critical signaling event, a helix in calcineurin Becomes bound and surrounded by calmodulin, thereby turning on calcineurin's serine/threonine phosphatase activity. Locating the calcineurin helix within a region of disorder is essential for enabling calmodulin to surround its target upon binding. (5) Calsequestrin regulates calcium levels in rite sarcoplasmic reticulum by binding approximately 50 ions/molecule. Disordered polyanion tails at the carboxy terminus bind many of these calcium ions, perhaps without adopting a unique structure. In addition to these examples, we will discuss 16 more proteins with native disorder. These disordered regions include molecular recognition domains, protein folding inhibitors, flexible linkers, entropic springs, entropic clocks, and entropic bristles. Motivated by such examples of intrinsic disorder we are studying the relationships between? amino acid sequence and order/disorder; and from this information Lye are predicting intrinsic order/disorder from amino acid sequence. The sequence-structure relationships indicate that disorder is an encoded property?, and the predictions strongly suggest that proteins in nature are much richer in intrinsic disorder than are those in the Protein Data Bank, Recent predictions on 29 genomes indicate that proteins from eucaryotes apparently have more intrinsic disorder than those from either bacteria or archaea, with typically > 30% of eucaryotic proteins having disorder-ed regions of length greater than or equal to 50 consecutive residues. (C) 2001 by Elsevier Science Inc.