Abstract

Among the enzyme lineages that undoubtedly emerged prior to the last universal common ancestor is the so-called HUP, which includes Class I aminoacyl tRNA synthetases (AARSs) as well as enzymes mediating NAD, FAD, and CoA biosynthesis. Here, we provide a detailed analysis of HUP evolution, from emergence to structural and functional diversification. The HUP is a nucleotide binding domain that uniquely catalyzes adenylation via the release of pyrophosphate. In contrast to other ancient nucleotide binding domains with the αβα sandwich architecture, such as P-loop NTPases, the HUP’s most conserved feature is not phosphate binding, but rather ribose binding by backbone interactions to the tips of β1 and/or β4. Indeed, the HUP exhibits unusual evolutionary plasticity and, while ribose binding is conserved, the location and mode of binding to the base and phosphate moieties of the nucleotide, and to the substrate(s) reacting with it, have diverged with time, foremost along the emergence of the AARSs. The HUP also beautifully demonstrates how a well-packed scaffold combined with evolvable surface elements promotes evolutionary innovation. Finally, we offer a scenario for the emergence of the HUP from a seed βαβ fragment, and suggest that despite an identical architecture, the HUP and the Rossmann represent independent emergences.

摘要

在最后一个普遍共同祖先之前出现的酶谱系中无疑是所谓的 HUP，它包括 I 类氨酰 tRNA 合成酶 (AARS) 以及介导 NAD、FAD 和 CoA 生物合成的酶。在这里，我们提供了 HUP 演变的详细分析，从出现到结构和功能多样化。HUP 是一个核苷酸结合结构域，通过释放焦磷酸来独特地催化腺苷酸化。与其他具有 αβα 三明治结构的古老核苷酸结合结构域（例如 P 环 NTPases）相比，HUP 最保守的特征不是磷酸盐结合，而是通过骨架相互作用与 β1 和/或 β4 尖端的核糖结合。事实上，HUP 表现出不同寻常的进化可塑性，虽然核糖结合是保守的，与核苷酸的碱基和磷酸基部分以及与其反应的底物的结合位置和模式随着时间的推移而不同，尤其是随着 AARS 的出现。HUP 还精美地展示了包装良好的支架与可进化的表面元素如何促进进化创新。最后，我们提供了从种子 βαβ 片段中出现 HUP 的场景，并建议尽管结构相同，但 HUP 和 Rossmann 代表独立的出现。