Structural highlights
Function
EI2BA_YEAST Acts as a non-essential regulatory component of the translation initiation factor 2B (eIF2-B or GCD complex), which catalyzes the exchange of eukaryotic initiation factor 2 (eIF-2)-bound GDP for GTP and is regulated by phosphorylated eIF-2. It activates the synthesis of GCN4 in yeast under amino acid starvation conditions by suppressing the inhibitory effects of multiple AUG codons present in the leader of GCN4 mRNA. It may promote either repression or activation of GCN4 expression depending on amino acid availability. Modulation of GCN3 regulatory function in response to amino acid availability occurs post-translationally.[1] [2]
Publication Abstract from PubMed
One of the responses to stress by eukaryotic cells is the down-regulation of protein synthesis by phosphorylation of translation initiation factor eIF2. Phosphorylation results in low availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting the interaction of eIF2 with its GTP-GDP exchange factor eIF2B. We have determined the cryo-EM structure of yeast eIF2B in complex with phosphorylated eIF2 at an overall resolution of 4.2 A. Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2alpha-D1, which contains the phosphorylated Ser51. eIF2alpha-D1 is mainly inserted between the N-terminal helix bundle domains of delta and alpha subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Balpha and indirectly by inducing contacts of eIF2alpha helix 58-63 with eIF2Bdelta leading to a competition with Met-tRNAi.
Structural basis for the inhibition of translation through eIF2alpha phosphorylation.,Gordiyenko Y, Llacer JL, Ramakrishnan V Nat Commun. 2019 Jun 14;10(1):2640. doi: 10.1038/s41467-019-10606-1. PMID:31201334[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cigan AM, Bushman JL, Boal TR, Hinnebusch AG. A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4. PMID:8506384
- ↑ Pavitt GD, Ramaiah KV, Kimball SR, Hinnebusch AG. eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange. Genes Dev. 1998 Feb 15;12(4):514-26. PMID:9472020
- ↑ Gordiyenko Y, Llacer JL, Ramakrishnan V. Structural basis for the inhibition of translation through eIF2alpha phosphorylation. Nat Commun. 2019 Jun 14;10(1):2640. doi: 10.1038/s41467-019-10606-1. PMID:31201334 doi:http://dx.doi.org/10.1038/s41467-019-10606-1
