Instituto de Biología Molecular y Celular de Rosario (IBR CONICET-UNR), Rosario, Argentina.
Plataforma de Biología Estructural y Metabolómica (PLABEM), Rosario, Argentina.
FEBS J. 2020 Feb;287(4):749-762. doi: 10.1111/febs.15016. Epub 2019 Aug 7.
The assembly of the Cu site in Cytochrome c Oxidase (COX) is a critical step for aerobic respiration in COX-dependent organisms. Several gene products have been associated with the assembly of this copper site, the most conserved of them belonging to the Sco family of proteins, which have been shown to perform different roles in different organisms. Plants express two orthologs of Sco proteins: Hcc1 and Hcc2. Hcc1 is known to be essential for plant development and for COX maturation, but its precise function has not been addressed until now. Here, we report the biochemical, structural and functional characterization of Arabidopsis thaliana Hcc1 protein (here renamed Sco1). We solved the crystal structure of the Cu -bound soluble domain of this protein, revealing a tri coordinated environment involving a CxxxCx H motif. We show that AtSco1 is able to work as a copper metallochaperone, inserting two Cu ions into the Cu site in a model of CoxII. We also show that AtSco1 does not act as a thiol-disulfide oxido-reductase. Overall, this information sheds new light on the biochemistry of Sco proteins, highlighting the diversity of functions among them despite their high structural similarities. DATABASE: PDB entry 6N5U (Crystal structure of Arabidopsis thaliana ScoI with copper bound).
细胞色素 c 氧化酶 (COX) 中 Cu 位点的组装是需氧呼吸的关键步骤，在依赖 COX 的生物体中。有几种基因产物与该铜位点的组装有关，其中最保守的属于 Sco 蛋白家族，它们在不同的生物体中表现出不同的功能。植物表达两种 Sco 蛋白的同源物：Hcc1 和 Hcc2。Hcc1 已知对植物发育和 COX 成熟至关重要，但直到现在其确切功能仍未得到解决。在这里，我们报告了拟南芥 Hcc1 蛋白（此处重命名为 Sco1）的生化、结构和功能特征。我们解决了该蛋白 Cu 结合可溶性结构域的晶体结构，揭示了一个涉及 CxxxCx H 基序的三配位环境。我们表明，AtSco1 能够作为铜金属伴侣蛋白，将两个 Cu 离子插入 CoxII 模型中的 Cu 位点。我们还表明，AtSco1 不作为硫醇-二硫键氧化还原酶。总的来说，这些信息为 Sco 蛋白的生物化学提供了新的见解，强调了它们之间功能的多样性，尽管它们具有高度的结构相似性。数据库：PDB 条目 6N5U（含铜的拟南芥 ScoI 晶体结构）。
