美国范德比尔特大学医学中心Eric P. Skaar团队和美国印第安纳大学David P. Giedroc团队共同合作，近期取得重要工作进展。他们研究发现锌调节的GTPase金属蛋白激活剂1（ZNG1）调节脊椎动物的锌稳态。该项研究成果2022年5月17日在线出版于《细胞》杂志上。
在这里，研究人员从功能上描述了一个在脊椎动物中保守的COG0523蛋白家族。他们将锌金属蛋白酶蛋氨酸氨基肽酶1(METAP1)鉴定为COG0523的激活底物，从而将这组COG0523蛋白重新命名为Zn 调节的GTPase金属蛋白激活剂 (ZNG1) 家族。通过使用生物化学、结构、遗传学和药理学的方法，研究了包括斑马鱼和小鼠在内的不同进化模型，研究人员证明了ZNG1蛋白在调节细胞锌稳态中的关键作用。总的来说，这些数据揭示了锌金属伴侣家族的存在，表明了ZNG1在细胞内Zn运输中的重要作用。
据了解，锌(Zn)是一种必需的微量营养素，是生物体中高达10%蛋白质的辅助因子。在锌限制期间，被称为金属伴侣的专门酶被预测将锌分配给特定的金属蛋白。这一功能被认为是由G3E GTPase COG0523蛋白发挥的，但目前还没有在任何生物体内通过实验鉴定出锌金属伴侣蛋白。
附：英文原文
Title: Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis
Author: Andy Weiss, Caitlin C. Murdoch, Katherine A. Edmonds, Matthew R. Jordan, Andrew J. Monteith, Yasiru R. Perera, Aslin M. Rodríguez Nassif, Amber M. Petoletti, William N. Beavers, Matthew J. Munneke, Sydney L. Drury, Evan S. Krystofiak, Kishore Thalluri, Hongwei Wu, Angela R.S. Kruse, Richard D. DiMarchi, Richard M. Caprioli, Jeffrey M. Spraggins, Walter J. Chazin, David P. Giedroc, Eric P. Skaar
Issue&Volume: 2022-05-17
Abstract: Zinc (Zn) is an essential micronutrient and cofactor for up to 10% of proteins inliving organisms. During Zn limitation, specialized enzymes called metallochaperonesare predicted to allocate Zn to specific metalloproteins. This function has been putativelyassigned to G3E GTPase COG0523 proteins, yet no Zn metallochaperone has been experimentallyidentified in any organism. Here, we functionally characterize a family of COG0523proteins that is conserved across vertebrates. We identify Zn metalloprotease methionineaminopeptidase 1 (METAP1) as a COG0523 client, leading to the redesignation of thisgroup of COG0523 proteins as the Zn-regulated GTPase metalloprotein activator (ZNG1)family. Using biochemical, structural, genetic, and pharmacological approaches acrossevolutionarily divergent models, including zebrafish and mice, we demonstrate a criticalrole for ZNG1 proteins in regulating cellular Zn homeostasis. Collectively, thesedata reveal the existence of a family of Zn metallochaperones and assign ZNG1 an importantrole for intracellular Zn trafficking.
DOI: 10.1016/j.cell.2022.04.011
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00458-5