Bellsolell Lluís, Cho-Park Park F, Poulin Francis, Sonenberg Nahum, Burley Stephen K
Laboratories of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
Structure. 2006 May;14(5):913-23. doi: 10.1016/j.str.2006.03.012.
The X-ray structure of the C-terminal region of human eukaryotic translation initiation factor 4G (eIF4G) has been determined at 2.2 A resolution, revealing two atypical HEAT-repeat domains. eIF4G recruits various translation factors and the 40S ribosomal subunit to the mRNA 5' end. In higher eukaryotes, the C terminus of eIF4G (4G/C) supports translational regulation by recruiting eIF4A, an RNA helicase, and Mnk1, the kinase responsible for phosphorylating eIF4E. Structure-guided surface mutagenesis and protein-protein interaction assays were used to identify binding sites for eIF4A and Mnk1 within the HEAT-repeats of 4G/C. p97/DAP5, a translational modulator homologous to eIF4G, lacks an eIF4A binding site in the corresponding region. The second atypical HEAT domain of the 4G/C binds Mnk1 using two conserved aromatic/acidic-box (AA-box) motifs. Within the first AA-box, the aromatic residues contribute to the hydrophobic core of the domain, while the acidic residues form a negatively charged surface feature suitable for electrostatic interactions with basic residues in Mnk1.
人类真核生物翻译起始因子4G（eIF4G）C端区域的X射线结构已在2.2埃分辨率下确定，揭示了两个非典型的HEAT重复结构域。eIF4G将各种翻译因子和40S核糖体亚基募集到mRNA的5'端。在高等真核生物中，eIF4G的C端（4G/C）通过募集RNA解旋酶eIF4A和负责磷酸化eIF4E的激酶Mnk1来支持翻译调控。利用结构导向的表面诱变和蛋白质-蛋白质相互作用分析来鉴定4G/C的HEAT重复序列内eIF4A和Mnk1的结合位点。p97/DAP5是一种与eIF4G同源的翻译调节因子，在相应区域缺乏eIF4A结合位点。4G/C的第二个非典型HEAT结构域利用两个保守的芳香/酸性框（AA框）基序结合Mnk1。在第一个AA框内，芳香族残基构成结构域的疏水核心，而酸性残基形成带负电荷的表面特征，适合与Mnk1中的碱性残基进行静电相互作用。
