Laboratory of Biochemistry, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41500, Larissa, Greece.
Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, Larissa, Greece.
Biochem Biophys Res Commun. 2024 Dec 20;739:150965. doi: 10.1016/j.bbrc.2024.150965. Epub 2024 Nov 9.
Hypoxia inducible factor 2α (HIF-2α) is a member of the basic helix-loop-helix(bHLH)-Per-Arnt-Sim (PAS) family of transcription factors. It is overexpressed in several cancers, associated with poor prognosis of the patients and resistance to treatment. Here, we study the residues 366-704 of the C-terminal end of human HIF-2α, which contains the N-transcriptional activation domain (NTAD), the oxygen-dependent degradation domain (ODD), and a part of the inhibitory domain (IH). An efficient protocol was developed to produce the 366-704 domain of human HIF-2α protein. Subsequently, we analyzed its biophysical characteristics using circular dichroism spectroscopy and size exclusion chromatography showing that the protein forms an antiparallel beta sheet conformation, and a computational model of the HIF-2α structure was produced. Our data offer new structural information for the unique biological properties of HIF-2α.
缺氧诱导因子 2α（HIF-2α）是碱性螺旋-环-螺旋（bHLH）-PAS 家族转录因子的成员之一。它在多种癌症中过度表达，与患者预后不良和治疗耐药有关。在这里，我们研究了人 HIF-2α C 端末端的 366-704 个残基，其中包含 N 转录激活结构域（NTAD）、氧依赖性降解结构域（ODD）和抑制结构域（IH）的一部分。开发了一种有效的方案来生产人 HIF-2α 蛋白的 366-704 结构域。随后，我们使用圆二色性光谱法和大小排阻色谱法分析了其生物物理特性，结果表明该蛋白形成反平行β片层构象，并构建了 HIF-2α 结构的计算模型。我们的数据为 HIF-2α 的独特生物学特性提供了新的结构信息。
