乙酰转移酶 NAA10 的色氨酸 38 位羟化不是人细胞中的酶开关。

Hydroxylation of the Acetyltransferase NAA10 Trp38 Is Not an Enzyme-Switch in Human Cells.

机构信息

Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.

Department of Immunotechnology, Lund University, Medicon Village, 22100 Lund, Sweden.

出版信息

Int J Mol Sci. 2021 Oct 30;22(21):11805. doi: 10.3390/ijms222111805.

DOI:10.3390/ijms222111805

PMID:34769235

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8583962/

Abstract

NAA10 is a major -terminal acetyltransferase (NAT) that catalyzes the cotranslational -terminal (Nt-) acetylation of 40% of the human proteome. Several reports of lysine acetyltransferase (KAT) activity by NAA10 exist, but others have not been able to find any NAA10-derived KAT activity, the latter of which is supported by structural studies. The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently found to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). In contrast, we could not detect hydroxylation of Trp38 of NAA10 in several human cell lines and found no evidence that NAA10 interacts with or is regulated by FIH. Our data suggest that NAA10 Trp38 hydroxylation is not a switch in human cells and that it alters its catalytic activity from a NAT to a KAT.

摘要

NAA10 是一种主要的末端乙酰转移酶（NAT），它催化 40%的人类蛋白质组的共翻译末端（Nt-）乙酰化。已经有几份关于 NAA10 的赖氨酸乙酰转移酶（KAT）活性的报告，但其他报告未能发现任何 NAA10 衍生的 KAT 活性，后者得到了结构研究的支持。最近发现，NAA10 对缺氧诱导因子 1α（HIF-1α）的 KAT 活性依赖于 NAA10 中色氨酸 38 位的羟化，由因子抑制 HIF-1α（FIH）完成。相比之下，我们在几种人类细胞系中未能检测到 NAA10 中色氨酸 38 位的羟化，也没有证据表明 NAA10 与 FIH 相互作用或受其调节。我们的数据表明，NAA10 色氨酸 38 位的羟化不是人类细胞中的开关，它将其催化活性从 NAT 转变为 KAT。