Graduate School of Pharmaceutical Science, Osaka University, Suita City, Osaka 565-0871, Japan.
Acta Crystallogr F Struct Biol Commun. 2023 Jul 1;79(Pt 7):169-179. doi: 10.1107/S2053230X2300523X. Epub 2023 Jun 26.
Superoxide dismutase (SOD) is an essential and ubiquitous antioxidant protein that is widely present in biological systems. The anhydrobiotic tardigrades are some of the toughest micro-animals. They have an expanded set of genes for antioxidant proteins such as SODs. These proteins are thought to play an essential role in oxidative stress resistance in critical situations such as desiccation, although their functions at the molecular level have yet to be explored. Here, crystal structures of a copper/zinc-containing SOD (RvSOD15) from an anhydrobiotic tardigrade, Ramazzottius varieornatus strain YOKOZUNA-1, are reported. In RvSOD15, one of the histidine ligands of the catalytic copper center is replaced by a valine (Val87). The crystal structures of the wild type and the V87H mutant show that even though a histidine is placed at position 87, a nearby flexible loop can destabilize the coordination of His87 to the Cu atom. Model structures of other RvSODs were investigated and it was found that some of them are also unusual SODs, with features such as deletion of the electrostatic loop or β3 sheet and unusual metal-binding residues. These studies show that RvSOD15 and some other RvSODs may have evolved to lose the SOD function, suggesting that gene duplications of antioxidant proteins do not solely explain the high stress tolerance of anhydrobiotic tardigrades.
超氧化物歧化酶(SOD)是一种重要且普遍存在的抗氧化蛋白,广泛存在于生物系统中。水熊虫是一些最顽强的微型动物。它们有一套扩展的抗氧化蛋白基因,如 SOD。这些蛋白质被认为在脱水等关键情况下的氧化应激抵抗中发挥着重要作用,尽管它们在分子水平上的功能尚未被探索。在这里,报道了一种来自水熊虫 Ramazzottius varieornatus 菌株 YOKOZUNA-1 的铜/锌结合 SOD(RvSOD15)的晶体结构。在 RvSOD15 中,催化铜中心的一个组氨酸配体被缬氨酸(Val87)取代。野生型和 V87H 突变体的晶体结构表明,尽管在位置 87 处放置了一个组氨酸,但附近的柔性环可以使 His87 与 Cu 原子的配位不稳定。还研究了其他 RvSOD 的模型结构,发现其中一些也是不寻常的 SOD,具有静电环或β3 片缺失和不寻常的金属结合残基等特征。这些研究表明,RvSOD15 和其他一些 RvSOD 可能已经进化为失去 SOD 功能,这表明抗氧化蛋白的基因重复并不完全解释水熊虫的高耐受力。