Biology Department, Brookhaven National Laboratory, Upton, NY, USA.
US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Nat Commun. 2024 Apr 12;15(1):3167. doi: 10.1038/s41467-024-47486-z.
Heme has a critical role in the chemical framework of the cell as an essential protein cofactor and signaling molecule that controls diverse processes and molecular interactions. Using a phylogenomics-based approach and complementary structural techniques, we identify a family of dimeric hemoproteins comprising a domain of unknown function DUF2470. The heme iron is axially coordinated by two zinc-bound histidine residues, forming a distinct two-fold symmetric zinc-histidine-iron-histidine-zinc site. Together with structure-guided in vitro and in vivo experiments, we further demonstrate the existence of a functional link between heme binding by Dri1 (Domain related to iron 1, formerly ssr1698) and post-translational regulation of succinate dehydrogenase in the cyanobacterium Synechocystis, suggesting an iron-dependent regulatory link between photosynthesis and respiration. Given the ubiquity of proteins containing homologous domains and connections to heme metabolism across eukaryotes and prokaryotes, we propose that DRI (Domain Related to Iron; formerly DUF2470) functions at the molecular level as a heme-dependent regulatory domain.
血红素在细胞的化学结构中起着至关重要的作用，作为一种必需的蛋白质辅因子和信号分子，它控制着多种过程和分子相互作用。我们使用基于系统发生基因组学的方法和互补的结构技术，鉴定了一类由两个锌结合的组氨酸残基轴向配位的二聚血红素蛋白家族，形成了一个独特的二倍对称锌-组氨酸-铁-组氨酸-锌结合位点。结合结构导向的体外和体内实验，我们进一步证明了 Dri1（与铁 1 相关的结构域，以前称为 ssr1698）与琥珀酸脱氢酶的翻译后调控之间存在功能联系，这表明在蓝藻 Synechocystis 中光合作用和呼吸作用之间存在铁依赖性的调节联系。鉴于含有同源结构域的蛋白质在真核生物和原核生物中广泛存在，并且与血红素代谢有关，我们提出 DRI（与铁相关的结构域；以前称为 DUF2470）在分子水平上作为血红素依赖性调节结构域发挥作用。
