幫助將抑制因子tRNA交付到核糖體的翻譯因子eIF2利用GTP水解的能量來發(fā)揮功能,。另一個因子eIF5已知在當eIF2與抑制因子tRNA和核糖體結(jié)合時會加快eIF2的GTP酶活性。在這項研究中,，研究人員確定了eIF5的另外兩個作用,。
一個涉及在eIF2上穩(wěn)定GDP（GTP水解的產(chǎn)物）；另一個涉及其通過磷酸化的eIF2來發(fā)揮作用,、以抑制鳥甙酸交換因子eIF2B,。這些結(jié)果澄清了我們對翻譯抑制怎樣被調(diào)控的認識。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09003
eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation
Martin D. Jennings & Graham D. Pavitt
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
In protein synthesis initiation, the eukaryotic translation initiation factor (eIF) 2 (a G protein) functions in its GTP-bound state to deliver initiator methionyl-tRNA (tRNAiMet) to the small ribosomal subunit and is necessary for protein synthesis in all cells1, 2. Phosphorylation of eIF2 [eIF2(αP)] is critical for translational control in diverse settings including nutrient deprivation, viral infection and memory formation3, 4, 5. eIF5 functions in start site selection as a GTPase accelerating protein (GAP) for the eIF2·GTP·tRNAiMet ternary complex within the ribosome-bound pre-initiation complex6, 7, 8. Here we define new regulatory functions of eIF5 in the recycling of eIF2 from its inactive eIF2·GDP state between successive rounds of translation initiation. First we show that eIF5 stabilizes the binding of GDP to eIF2 and is therefore a bi-functional protein that acts as a GDP dissociation inhibitor (GDI). We find that this activity is independent of the GAP function and identify conserved residues within eIF5 that are necessary for this role. Second we show that eIF5 is a critical component of the eIF2(αP) regulatory complex that inhibits the activity of the guanine-nucleotide exchange factor (GEF) eIF2B. Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls.
