Algire Mikkel A, Maag David, Lorsch Jon R
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Cell. 2005 Oct 28;20(2):251-62. doi: 10.1016/j.molcel.2005.09.008.
Irreversible GTP hydrolysis by eIF2 is a critical step in translation initiation in eukaryotes because it is thought to commit the translational machinery to assembling the ribosomal complex at the selected point in the mRNA. Our quantitative analysis of the steps and interactions involved in activating GTP hydrolysis by eIF2 during translation initiation in vitro indicates that a structural rearrangement in the 43S preinitiation complex activates it to become fully competent to hydrolyze GTP. Contrary to the prevailing model, release of inorganic phosphate after GTP hydrolysis by eIF2, not hydrolysis itself, is controlled by recognition of the AUG codon. Release of P(i), which makes GTP hydrolysis irreversible, appears to be controlled by the AUG-dependent dissociation of eIF1 from the preinitiation complex.
真核生物中，eIF2介导的不可逆GTP水解是翻译起始的关键步骤，因为它被认为能促使翻译机制在mRNA的选定位置组装核糖体复合物。我们对体外翻译起始过程中eIF2激活GTP水解所涉及的步骤和相互作用进行的定量分析表明，43S起始前复合物中的结构重排激活了它，使其完全具备水解GTP的能力。与普遍模型相反，eIF2水解GTP后无机磷酸的释放，而非水解本身，受AUG密码子识别的控制。使GTP水解不可逆的无机磷酸（Pi）的释放，似乎受eIF1从起始前复合物中AUG依赖的解离控制。
