Natural history of the E1-like superfamily: implication for adenylation, sulfur transfer, and ubiquitin conjugation.
Natural history of the E1-like superfamily: implication for adenylation, sulfur transfer, and ubiquitin conjugation.
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DOI：
10.1002/prot.22298
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发表时间：
2009-06
影响因子：
2.9
通讯作者：
Aravind, L.
中科院分区：
文献类型：
--
作者：
Burroughs, A. Maxwell;Iyer, Lakshminarayan M.;Aravind, L.
关键词：
E1样超家族是泛素(Ub)结合、半胱氨酸、硫胺素、MoCo和几种次生代谢物生物合成的中心。然而，它的功能多样性和进化史还没有被很好地理解。我们发展了这个超家族的自然分类，并用它来破译在E1样超家族进化中发生的主要适应趋势。在Rossmann折叠中，E1样蛋白与依赖于NAD(P)/FAD的脱氢酶和依赖于S的甲基转移酶最为接近。因此，它们的磷转移活性是相对于其他Rossmannoid褶皱中所见的此类活性而言的一项独立的催化“发明”。序列和结构分析揭示了不同的E1样家族之间参与腺化、硫代转移和底物结合的残基和结构的显著差异，使我们能够预测以前未知的功能适应。E1样蛋白被融合到几个先前未检测到的结构域，如预测的硫转移结构域，包含一个新的TATA结合蛋白折叠超家族，不同类型的催化域，一个新的有翼螺旋-转角-螺旋结构域，以及与Ub结合相关的潜在适配域。在这些融合的基础上，我们开发了一个将E1催化的腺基化/硫代化与进一步的下游反应联系起来的通用模型。这可能涉及到E1活性位点和不同融合的C-末端结构域之间的动态相互作用。我们还预测了E1样结构域参与了以前未描述的细菌次生代谢途径、新的半胱氨酸生物合成系统，如与古生代O-磷酸丝氨酸tRNA相关的系统、金属-硫簇组装(例如，在固氮中)和Ub-结合。进化重建表明，最后一个通用共同祖先(LUCA)含有单一的E1样结构域，既具有磷酸转移活性，又具有硫代转移活性，并参与多种硫转移反应。类似于E1超家族随后扩大到包括聚集在三个主要辐射中的26个家族。它们广泛参与泛素激活、辅因子和半胱氨酸的生物合成以及次生代谢物的生物合成。有鉴于此，我们提出的证据表明，在真核生物中，其他类似E1的酶，如Urm1，是独立招募用于Ub1结合的，可能没有传统的类E2酶发挥作用。
The E1-like superfamily is central to ubiquitin (Ub) conjugation, biosynthesis of cysteine, thiamine and MoCo and several secondary metabolites. Yet, its functional diversity and evolutionary history is not well-understood. We develop a natural classification of this superfamily and use it to decipher the major adaptive trends occurring in the evolution of the E1-like superfamily. Within the Rossmann fold, E1-like proteins are closest to NAD(P)/FAD-dependent dehydrogenases and S-AdoMet-dependent methyltransferases. Hence, their phosphotransfer activity is an independent catalytic “invention” with respect to such activities seen in other Rossmannoid folds. Sequence and structure analysis reveals a striking diversity of residues and structures involved in adenylation, sulfotransfer and substrate-binding between different E1-like families, allowing us to predict previously uncharacterized functional adaptations. E1-like proteins are fused to several previously undetected domains, such as a predicted sulfur transfer domain containing a novel superfamily of the TATA-binding protein fold, different types of catalytic domains, a novel winged helix-turn-helix domain and potential adaptor domains related to Ub conjugation. Based on these fusions we develop a generalized model for the linking of E1 catalyzed adenylation/thiolation with further down-stream reactions. This is likely to involve a dynamic interplay between the E1 active sites and diverse fused C-terminal domains. We also predict participation of E1-like domains in previously uncharacterized bacterial secondary metabolism pathways, new cysteine biosynthesis systems, such as those associated with archaeal O-phosphoseryl tRNA, metal-sulfur cluster assembly (e.g. in nitrogen fixation) and Ub-conjugation. Evolutionary reconstructions suggest that the last universal common ancestor (LUCA) contained a single E1-like domain possessing both phosphotransfer and thiolating activities and participating in multiple sulfotransfer reactions. The E1-like superfamily subsequently expanded to include 26 families clustering into three major radiations. These are broadly involved in ubiquitin activation, cofactor and cysteine biosynthesis, and biosynthesis of secondary metabolites. In light of this we present evidence that in eukaryotes other E1-like enzymes, such as Urm1, were independently recruited for Ubl conjugation, probably functioning without conventional E2-like enzymes.
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