6i7t

Structural highlights

Function

[IF2A_YEAST] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [EI2BB_YEAST] Acts as a 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. GCD6 and GCD7 repress GCN4 expression at the translational level by ensuring that ribosomes which have translated UORF1 will reinitiate at UORF2, -3, or -4 and thus fail to reach the GCN4 start site.^{[1] [2]} [IF2B_YEAST] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [EI2BD_YEAST] Acts as essential 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. GCD2 is also required for cell viability. Its function can partially be replaced by GCN3 under normal growth conditions in GCD2-defective mutants, under AA starvation conditions GCN3 is an antagonist (GCN4 translational activator).^{[3] [4]} [IF2G_YEAST] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [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.^{[5] [6]} [EI2BE_YEAST] Acts as a catalytic 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. GCD6 and GCD7 repress GCN4 expression at the translational level by ensuring that ribosomes which have translated UORF1 will reinitiate at UORF2, -3, or -4 and thus fail to reach the GCN4 start site.^{[7] [8]} [EI2BG_YEAST] Acts as essential 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. GCD1 stabilizes the interaction between eIF-2 and GCD6 and stimulates the catalytic activity in vitro.^{[9] [10]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ 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
8. ↑ 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
9. ↑ 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
10. ↑ 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
11. ↑ Adomavicius T, Guaita M, Zhou Y, Jennings MD, Latif Z, Roseman AM, Pavitt GD. The structural basis of translational control by eIF2 phosphorylation. Nat Commun. 2019 May 13;10(1):2136. doi: 10.1038/s41467-019-10167-3. PMID:31086188 doi:http://dx.doi.org/10.1038/s41467-019-10167-3