The case for a common ancestor: kinesin and myosin motor proteins and G proteins
The case for a common ancestor: kinesin and myosin motor proteins and G proteins
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DOI：
10.1023/a:1005489907021
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发表时间：
1998-11-01
影响因子：
2.7
通讯作者：
Fletterick, RJ
中科院分区：
文献类型：
--
作者：
Kull, FJ;Vale, RD;Fletterick, RJ
最近的研究表明，驱动蛋白和肌球蛋白的运动结构域之间存在令人惊讶的结构和功能相似性。运动蛋白和 G 蛋白的共同特征也已被描述。尽管有这些相似之处，但这些蛋白质之间的进化关系，甚至运动蛋白之间的进化关系并不明显，因为这些转导蛋白质中核心重叠结构元件的拓扑连接性彼此不相同。使用二级结构拓扑、功能域和活性位点化学的比较作为相关性的标准，我们提出了一套规则来确定几乎没有或没有序列同一性的蛋白质之间的潜在进化关系。这些规则用于探索驱动蛋白和肌球蛋白之间的进化关系，以及运动蛋白和其他含有核苷酸结合蛋白的磷酸环（P 环）之间的进化关系。我们证明驱动蛋白和肌球蛋白在活性位点内外表现出显着的化学保守性，并提出了一种从假设的祖先蛋白质产生各自拓扑的进化方案。我们还表明，与各种其他含有 P 环的蛋白质相比，细胞骨架马达在拓扑结构和活性位点化学方面与 G 蛋白最相似。我们得出结论，驱动蛋白和肌球蛋白，可能还有 G 蛋白，可能通过共同核心核苷酸结合基序的发散进化直接相关，并描述了该祖先的可能拓扑结构。这些蛋白质使用类似的化学和物理机制来感知活性位点中结合的核苷酸的状态，然后将这些变化传递给蛋白质伙伴。不同的拓扑结构可以通过独特的遗传插入来解释，这些插入添加到祖蛋白结构的边缘并且不破坏疏水核心。 (C) Kluwer 学术出版社。
Recent studies have shown surprising structural and functional similarities between the motor domains of kinesin and myosin. Common features have also been described for motor proteins and G proteins. Despite these similarities, the evolutionary relationships between these proteins, even among the motor proteins, has not been obvious, since the topological connectivities of the core overlapping structural elements in these transducing proteins are not identical to one another. Using secondary structure topology, comparison of functional domains and active site chemistry as criteria for relatedness, we propose a set of rules for determining potential evolutionary relationships between proteins showing little or no sequence identity. These rules were used to explore the evolutionary relationship between kinesin and myosin, as well as between motor proteins and other phosphate-loop (P-loop) containing nucleotide-binding proteins. We demonstrate that kinesin and myosin show significant chemical conservations within and outside of the active site, and present an evolutionary scheme that produces their respective topologies from a hypothetical ancestral protein. We also show that, when compared with various other P-loop-containing proteins, the cytoskeletal motors are most similar to G proteins with respect to topology and active site chemistry. We conclude that kinesin and myosin, and possibly G proteins, are probably directly related via divergent evolution from a common core nucleotide-binding motif, and describe the likely topology of this ancestor. These proteins use similar chemical and physical mechanisms to both sense the state of the nucleotide bound in the active site, and then transmit these changes to protein partners. The different topologies can be accounted for by unique genetic insertions that add to the edge of a progenitor protein structure and do not disrupt the hydrophobic core. (C) Kluwer Academic Publishers.