Kim K K, Hung L W, Yokota H, Kim R, Kim S H
Physical Biosciences Division of Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10419-24. doi: 10.1073/pnas.95.18.10419.
Eukaryotic translation initiation factor 5A (eIF-5A) is a ubiquitous protein found in all eukaryotic cells. The protein is closely associated with cell proliferation in the G1-S stage of the cell cycle. Recent findings show that the eIF-5A proteins are highly expressed in tumor cells and act as a cofactor of the Rev protein in HIV-1-infected cells. The mature eIF is the only protein known to have the unusual amino acid hypusine, a post-translationally modified lysine. The crystal structure of eIF-5A from Methanococcus jannaschii (MJ eIF-5A) has been determined at 1.9 A and 1.8 A resolution in two crystal forms by using the multiple isomorphous replacement method and the multiwavelength anomalous diffraction method for the first crystal form and the molecular replacement method for the second crystal form. The structure consists of two folding domains, one of which is similar to the oligonucleotide-binding domain found in the prokaryotic cold shock protein and the translation initiation factor IF1 despite the absence of any significant sequence similarities. The 12 highly conserved amino acid residues found among eIF-5As include the hypusine site and form a long protruding loop at one end of the elongated molecule.
真核生物翻译起始因子5A（eIF-5A）是一种在所有真核细胞中都存在的普遍蛋白质。该蛋白质在细胞周期的G1-S期与细胞增殖密切相关。最近的研究结果表明，eIF-5A蛋白在肿瘤细胞中高度表达，并在HIV-1感染的细胞中作为Rev蛋白的辅助因子发挥作用。成熟的eIF是已知唯一含有异常氨基酸hypusine（一种翻译后修饰的赖氨酸）的蛋白质。通过使用多重同晶置换法和多波长反常衍射法（用于第一种晶体形式）以及分子置换法（用于第二种晶体形式），已分别以1.9埃和1.8埃的分辨率确定了嗜压甲烷球菌的eIF-5A（MJ eIF-5A）的两种晶体形式的晶体结构。该结构由两个折叠结构域组成，其中一个结构域与原核生物冷休克蛋白和翻译起始因子IF1中发现的寡核苷酸结合结构域相似，尽管它们之间没有任何明显的序列相似性。在eIF-5A中发现的12个高度保守的氨基酸残基包括hypusine位点，并在细长分子的一端形成一个长的突出环。
