School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.
NASA Center for the Origin of Life, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Nucleic Acids Res. 2020 Sep 4;48(15):8663-8674. doi: 10.1093/nar/gkaa586.
Divalent metal cations are essential to the structure and function of the ribosome. Previous characterizations of the ribosome performed under standard laboratory conditions have implicated Mg2+ as a primary mediator of ribosomal structure and function. Possible contributions of Fe2+ as a ribosomal cofactor have been largely overlooked, despite the ribosome's early evolution in a high Fe2+ environment, and the continued use of Fe2+ by obligate anaerobes inhabiting high Fe2+ niches. Here, we show that (i) Fe2+ cleaves RNA by in-line cleavage, a non-oxidative mechanism that has not previously been shown experimentally for this metal, (ii) the first-order in-line rate constant with respect to divalent cations is >200 times greater with Fe2+ than with Mg2+, (iii) functional ribosomes are associated with Fe2+ after purification from cells grown under low O2 and high Fe2+ and (iv) a small fraction of Fe2+ that is associated with the ribosome is not exchangeable with surrounding divalent cations, presumably because those ions are tightly coordinated by rRNA and deeply buried in the ribosome. In total, these results expand the ancient role of iron in biochemistry and highlight a possible new mechanism of iron toxicity.
二价金属阳离子对核糖体的结构和功能至关重要。以前在标准实验室条件下对核糖体进行的特性描述表明，Mg2+ 是核糖体结构和功能的主要介导物。尽管核糖体在高 Fe2+ 环境中早期进化，并且必需的厌氧菌在高 Fe2+ 生境中仍继续使用 Fe2+，但 Fe2+ 作为核糖体辅因子的可能贡献在很大程度上被忽视了。在这里，我们表明：(i) Fe2+ 通过直链切割使 RNA 断裂，这是一种以前未在该金属上通过实验证明的非氧化机制；(ii) 与 Mg2+ 相比，Fe2+ 与二价阳离子的一级直链速率常数高 200 多倍；(iii) 在低 O2 和高 Fe2+ 条件下生长的细胞中，从细胞中纯化出的功能核糖体与 Fe2+ 相关；(iv) 与核糖体相关的 Fe2+ 的一小部分不可与周围的二价阳离子交换，大概是因为这些离子被 rRNA 紧密配位并且深埋在核糖体中。总的来说，这些结果扩展了铁在生物化学中的古老作用，并强调了铁毒性的一种新的可能机制。
