The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.
The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.
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Tim Barrel结构促进了蛋白质介导的代谢的早期演变。
DOI：
10.1007/s00239-015-9722-8
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发表时间：
2016-01
影响因子：
3.9
通讯作者：
Landweber LF
中科院分区：
文献类型：
--
作者：
Goldman AD;Beatty JT;Landweber LF
磷酸丙糖异构酶(TIM)桶蛋白折叠是一个结构重复的结构，存在于大约10%的所有酶中。一般认为，这种在现代蛋白质组中的普遍存在反映了在早期蛋白质介导的新陈代谢中的重要历史作用。在这里，我们提供了定量和比较分析，以支持关于TIM Barrel体系结构早期重要性的几个假设。蛋白质结构的信息论分析支持这样的假设，即与其他混合α/β结构相比，TIM桶结构更容易通过复制和重组而出现。我们发现，与分类学上最广泛的超家族相对应的Tim Barrel酶也具有最广泛的功能，通常受到金属和核苷酸衍生的辅因子的辅助，这些辅因子被认为反映了代谢进化的早期阶段。通过与其他推测古老的蛋白质结构的比较，我们发现TIM桶蛋白的功能多样性不能简单地用它们的古老来解释。相反，TIM桶功能的广度可以部分地解释为加入了广泛的辅因子，这一趋势似乎并不普遍存在于蛋白质中。这些结果支持这样的假设，即简单而功能通用的TIM桶结构可能在蛋白质生物合成的进化早期就已经出现，并为促进核酶、多肽和地化催化剂向现代蛋白质酶的代谢转变提供了理想的支架。本文的在线版本(doi：10.1007/s00239-0159722-8)包含补充材料，授权用户可以使用。
The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10 % of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes. The online version of this article (doi:10.1007/s00239-015-9722-8) contains supplementary material, which is available to authorized users.