Marcotrigiano J, Gingras A C, Sonenberg N, Burley S K
Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA.
Nucleic Acids Symp Ser. 1997(36):8-11.
The X-ray structure of the eukaryotic translation initiation factor 4E (eIF4E), bound to 7-methyl-GDP, has been determined at 2.2A resolution. eIF4E recognizes 5' 7-methyl-G(5')ppp(5')N mRNA caps during the rate-limiting initiation step of translation. The protein resembles a cupped hand, and consists of a curved, 8-stranded antiparallel beta-sheet, backed by three long alpha-helices. 7-methyl-GDP binds in a narrow cap-binding slot on the molecule's concave surface, where 7-methyl-guanine recognition is mediated by base sandwiching between two conserved tryptophans, plus formation of three hydrogen bonds and a van der Waals contact between its N7-methyl group and a third conserved tryptophan. Additional protein-ligand interactions include salt bridges and hydrogen bonds, plus water-mediated hydrogen bonds. The observed mode of 5' m-RNA cap recognition is almost certainly conserved among all known eIF4Es.
真核生物翻译起始因子4E（eIF4E）与7-甲基-GDP结合的X射线结构已在2.2埃分辨率下确定。在翻译的限速起始步骤中，eIF4E识别5' 7-甲基-G(5')ppp(5')N mRNA帽。该蛋白质形似一个杯状的手，由一个弯曲的8股反平行β-折叠组成，后面有三个长α-螺旋。7-甲基-GDP结合在分子凹面上一个狭窄的帽结合槽中，其中7-甲基鸟嘌呤的识别是通过两个保守色氨酸之间的碱基夹层介导的，加上形成三个氢键以及其N7-甲基基团与第三个保守色氨酸之间的范德华接触。额外的蛋白质-配体相互作用包括盐桥和氢键，以及水介导的氢键。在所有已知的eIF4E中，观察到的5' mRNA帽识别模式几乎肯定是保守的。
