Department of Microbiology, University of Georgia, Athens, Georgia, USA.
Department of Microbiology, University of Georgia, Athens, Georgia, USA
Microbiol Mol Biol Rev. 2020 Jul 15;84(3). doi: 10.1128/MMBR.00024-20. Print 2020 Aug 19.
The Rid (YjgF/YER057c/UK114) protein superfamily was first defined by sequence homology with available protein sequences from bacteria, archaea, and eukaryotes (L. Parsons, N. Bonander, E. Eisenstein, M. Gilson, et al., Biochemistry 42:80-89, 2003, https://doi.org/10.1021/bi020541w). The archetypal subfamily, RidA (reactive intermediate deaminase A), is found in all domains of life, with the vast majority of free-living organisms carrying at least one RidA homolog. In over 2 decades, close to 100 reports have implicated Rid family members in cellular processes in prokaryotes, yeast, plants, and mammals. Functional roles have been proposed for Rid enzymes in amino acid biosynthesis, plant root development and nutrient acquisition, cellular respiration, and carcinogenesis. Despite the wealth of literature and over a dozen high-resolution structures of different RidA enzymes, their biochemical function remained elusive for decades. The function of the RidA protein was elucidated in a bacterial model system despite (i) a minimal phenotype of mutants, (ii) the enzyme catalyzing a reaction believed to occur spontaneously, and (iii) confusing literature on the pleiotropic effects of RidA homologs in prokaryotes and eukaryotes. Subsequent work provided the physiological framework to support the RidA paradigm in by linking the phenotypes of mutants lacking to the accumulation of the reactive metabolite 2-aminoacrylate (2AA), which damaged metabolic enzymes. Conservation of enamine/imine deaminase activity of RidA enzymes from all domains raises the likelihood that, despite the diverse phenotypes, the consequences when RidA is absent are due to accumulated 2AA (or a similar reactive enamine) and the diversity of metabolic phenotypes can be attributed to differences in metabolic network architecture. The discovery of the RidA paradigm in laid a foundation for assessing the role of Rid enzymes in diverse organisms and contributed fundamental lessons on metabolic network evolution and diversity in microbes. This review describes the studies that defined the conserved function of RidA, the paradigm of enamine stress in , and emerging studies that explore how this paradigm differs in other organisms. We focus primarily on the RidA subfamily, while remarking on our current understanding of the other Rid subfamilies. Finally, we describe the current status of the field and pose questions that will drive future studies on this widely conserved protein family to provide fundamental new metabolic information.
Rid (YjgF/YER057c/UK114) 蛋白超家族最初是根据来自细菌、古菌和真核生物的可用蛋白质序列的序列同源性定义的（L. Parsons、N. Bonander、E. Eisenstein、M. Gilson 等人，生物化学 42:80-89, 2003, https://doi.org/10.1021/bi020541w）。原型亚家族 RidA（反应中间体脱氨酶 A）存在于所有生命领域，绝大多数自由生活的生物体至少携带一个 RidA 同源物。在过去的 20 多年里，近 100 份报告表明 Rid 家族成员参与了原核生物、酵母、植物和哺乳动物的细胞过程。已经提出 Rid 酶在氨基酸生物合成、植物根发育和养分获取、细胞呼吸和致癌作用中的功能作用。尽管文献丰富，并且有十多个不同 RidA 酶的高分辨率结构，但它们的生化功能在几十年内仍然难以捉摸。尽管存在以下情况，但 RidA 蛋白的功能在细菌模型系统中得到了阐明：（i） 突变体的表型最小，（ii） 酶催化被认为自发发生的反应，以及（iii） 关于 RidA 同源物在原核生物和真核生物中的多效性效应的混乱文献。随后的工作为通过将缺乏 的突变体的表型与积累的反应性代谢物 2-氨基丙烯酸（2AA）联系起来，为 中的 RidA 范例提供了生理框架，2AA 损害了代谢酶。来自所有领域的 RidA 酶的烯胺/亚胺脱氨酶活性的保守性提高了这样的可能性，即尽管表型不同，但当 RidA 缺失时，后果是由于积累的 2AA（或类似的反应性烯胺），并且代谢表型的多样性可以归因于代谢网络结构的差异。在 中发现 RidA 范例为评估 Rid 酶在不同生物体中的作用奠定了基础，并为微生物代谢网络进化和多样性提供了基本的经验教训。这篇综述描述了定义 RidA 保守功能、 在 中的烯胺应激范例以及探索该范例在其他生物体中如何不同的研究。我们主要关注 RidA 亚家族，同时评论我们目前对其他 Rid 亚家族的理解。最后，我们描述了该领域的现状，并提出了将推动未来对这个广泛保守的蛋白质家族的研究的问题，以提供新的基本代谢信息。
