Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Cell Rep. 2022 May 17;39(7):110834. doi: 10.1016/j.celrep.2022.110834.
The evolution of zinc (Zn) as a protein cofactor altered the functional landscape of biology, but dependency on Zn also created an Achilles' heel, necessitating adaptive mechanisms to ensure Zn availability to proteins. A debated strategy is whether metallochaperones exist to prioritize essential Zn-dependent proteins. Here, we present evidence for a conserved family of putative metal transferases in human and fungi, which interact with Zn-dependent methionine aminopeptidase type I (MetAP1/Map1p/Fma1). Deletion of the putative metal transferase in Saccharomyces cerevisiae (ZNG1; formerly YNR029c) leads to defective Map1p function and a Zn-deficiency growth defect. In vitro, Zng1p can transfer Zn or Co to apo-Map1p, but unlike characterized copper chaperones, transfer is dependent on GTP hydrolysis. Proteomics reveal mis-regulation of the Zap1p transcription factor regulon because of loss of ZNG1 and Map1p activity, suggesting that Zng1p is required to avoid a compounding effect of Map1p dysfunction on survival during Zn limitation.
锌（Zn）作为蛋白质辅因子的进化改变了生物学的功能格局，但对 Zn 的依赖也形成了一个致命弱点，需要适应机制来确保蛋白质获得 Zn。一个有争议的策略是，是否存在金属伴侣来优先考虑必需的 Zn 依赖性蛋白质。在这里，我们提出了在人和真菌中存在保守的假定金属转移酶家族的证据，它们与 Zn 依赖性蛋氨酸氨肽酶 I（MetAP1/Map1p/Fma1）相互作用。酿酒酵母（ZNG1；以前称为 YNR029c）中假定金属转移酶的缺失导致 Map1p 功能缺陷和 Zn 缺乏生长缺陷。在体外，Zng1p 可以将 Zn 或 Co 转移到 apo-Map1p，但与表征的铜伴侣不同，转移依赖于 GTP 水解。蛋白质组学揭示了 Zap1p 转录因子调控因子的失调，因为 ZNG1 和 Map1p 活性的丧失，这表明需要 Zng1p 来避免 Map1p 功能障碍在 Zn 限制期间对生存产生叠加效应。
