A variety of cellular processes rely on G-proteins, which cycle through active GTP-bound and inactive GDP-bound forms. The switch between these states is commonly regulated by GEFs (guanine-nucleotide-exchange factors) and GAPs (GTPase-activating proteins). Although G-proteins have structural similarity, GEFs are very diverse proteins. A complex example of this system is seen in eukaryotic translation initiation between eIF (eukaryotic initiation factor) 2, a G-protein, its five-subunit GEF, eIF2B, and its GAP, eIF5. eIF2 delivers Met-tRNAi (initiator methionyl-tRNA) to the 40S ribosomal subunit before mRNA binding. Upon AUG recognition, eIF2 hydrolyses GTP, aided by eIF5. eIF2B then re-activates eIF2 by removing GDP, thereby promoting association of GTP. In the present article, we review data from studies of representative G-protein–GEF pairs and compare these with observations from our research on eIF2 and eIF2B to propose a model for how interactions between eIF2B and eIF2 promote guanine nucleotide exchange.
Clues to the mechanism of action of eIF2B, the guanine-nucleotide-exchange factor for translation initiation
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Sarah S. Mohammad-Qureshi, Martin D. Jennings, Graham D. Pavitt; Clues to the mechanism of action of eIF2B, the guanine-nucleotide-exchange factor for translation initiation. Biochem Soc Trans 1 August 2008; 36 (4): 658–664. doi: https://doi.org/10.1042/BST0360658
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