Structural evolution of the protein kinase-like superfamily.
Structural evolution of the protein kinase-like superfamily.
复制标题
蛋白激酶样超家族的结构进化。
DOI：
10.1371/journal.pcbi.0010049
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发表时间：
2005-10
影响因子：
4.3
通讯作者：
Bourne, PE
中科院分区：
文献类型：
--
作者：
Scheeff, ED;Bourne, PE
蛋白激酶家族是一个庞大而重要的家族，但它只是一个更大的同源激酶超家族中的一个家族，该家族磷酸化各种底物，并在所有三个生命超王国中发挥重要作用。我们使用了精心构建的选定的激酶的结构对齐作为蛋白激酶样超家族的结构进化的研究的基础。结构的比较揭示了一个“通用核心”结构域，仅由ATP结合和磷酸转移反应所需的区域组成。值得注意的是，即使在通用核心中，一些激酶结构也显示出显著的变化，同时仍然保留了基本的活性。因此，蛋白激酶样超家族在漫长的进化时间尺度上经历了大量的结构和序列修改。我们构建了一个系统发育树的超家族使用一种新的方法，允许结合序列和结构信息到一个统一的定量分析。当考虑到物种分布和其他指标的背景下，我们的树提供了一个令人信服的情况下，从一个共享的共同祖先的各种激酶家族的发展。我们提出，大多数所谓的“非典型激酶”不是间歇性地来自蛋白激酶，而是在进化早期分化形成一个独特的系统群。在非典型激酶中，氨基糖苷类和胆碱激酶家族似乎具有最密切的关系。这两个家族反过来似乎是最密切相关的蛋白激酶家族。此外，我们的分析表明，actin-fragmin激酶，一种非典型的蛋白激酶，是更密切相关的磷酸肌醇-3激酶家族比蛋白激酶家族。两个最不同的家族，α-激酶和磷脂酰肌醇磷酸激酶（PIPK），似乎具有不同的进化历史。虽然PIPKs可能与激酶超家族的其他成员有进化关系，但这种关系似乎非常遥远（可能是间接的）。相反，α-激酶似乎是非典型激酶早期分化的一个例外：它们显然是最近在真核生物中出现的。我们提出了从现存的激酶折叠衍生α-激酶的可能方案。大多数蛋白质具有独特的三维结构，这决定了它们的大部分功能。相关的蛋白质通常具有相似的结构，这是由于它们共享的遗传遗产和（通常）相似的功能。因此，我们可以说蛋白质的“家族”曾经共享一个共同的祖先基因，但在进化的过程中已经分化成具有相似但改变的序列的不同形式。在某些情况下，这种序列差异可能会发生，以至于蛋白质的结构实际上开始改变，形成远亲蛋白质的“超家族”。传统上，蛋白质进化中的事件是通过构建基于蛋白质序列之间的相似性的进化树来研究的。然而，在超家族水平上，序列相似性减弱到构建准确的树变得更加困难的程度。这项工作试图通过将结构相似性信息整合到分析中来解决这个问题。由于蛋白质结构的变化比序列慢得多，结构相似性提供了关于蛋白质之间关系的强有力信号。当这种新形式的树与其他进化信息一起考虑时，作者能够为重要的蛋白激酶样超家族的大部分进化提供可支持的历史。
The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase–like superfamily. The comparison of structures revealed a “universal core” domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase–like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called “atypical kinases” are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, α-kinases and phosphatidylinositol phosphate kinases (PIPKs), appear to have distinct evolutionary histories. While the PIPKs probably have an evolutionary relationship with the rest of the kinase superfamily, the relationship appears to be very distant (and perhaps indirect). Conversely, the α-kinases appear to be an exception to the scenario of early divergence for the atypical kinases: they apparently arose relatively recently in eukaryotes. We present possible scenarios for the derivation of the α-kinases from an extant kinase fold. Most proteins have distinct three-dimensional structures that determine much of their functional capability. Proteins that are related usually have similar structures, owing to their shared genetic heritage and (often) similar function. Hence, one can speak of “families” of proteins that at one time all shared a common ancestor gene, but have diverged over eons of evolution into distinct forms with similar but altered sequences. In some cases, this sequence divergence can occur to the point that the structures of the proteins actually begin to change, forming “superfamilies” of distantly related proteins. Traditionally, events in protein evolution are investigated through the construction of evolutionary trees based on similarity between protein sequences. However, at the superfamily level sequence similarity weakens to the point that building accurate trees becomes much more problematic. This work attempts to address this problem by integrating structural similarity information into the analysis. Because protein structure changes much more slowly than sequence, structural similarity provides powerful signals about the relationships between proteins. When this new form of tree is considered alongside other evolutionary information, the authors are able to provide a supportable history for much of the evolution of the important protein kinase–like superfamily.
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