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| | <SX load='6i3m' size='340' side='right' viewer='molstar' caption='[[6i3m]], [[Resolution|resolution]] 3.93Å' scene=''> | | <SX load='6i3m' size='340' side='right' viewer='molstar' caption='[[6i3m]], [[Resolution|resolution]] 3.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i3m]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3M OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6I3M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i3m]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I3M FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.93Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GCN3, AAS2, TIF221, YKR026C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), GCD2, TIF224, YGR083C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), GCD7, TIF222, YLR291C, L8003.17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), GCD6, TIF225, YDR211W, YD8142.12, YD8142B.03 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), GCD1, TIF223, TRA3, YOR260W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), SUI2, TIF211, YJR007W, J1429 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), SUI3, TIF212, YPL237W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), GCD11, TIF213, YER025W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6i3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3m OCA], [http://pdbe.org/6i3m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i3m RCSB], [http://www.ebi.ac.uk/pdbsum/6i3m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3m ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6i3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3m OCA], [https://pdbe.org/6i3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i3m RCSB], [https://www.ebi.ac.uk/pdbsum/6i3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IF2A_YEAST 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. [[http://www.uniprot.org/uniprot/EI2BB_YEAST 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.<ref>PMID:8506384</ref> <ref>PMID:9472020</ref> [[http://www.uniprot.org/uniprot/IF2B_YEAST 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. [[http://www.uniprot.org/uniprot/EI2BD_YEAST 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).<ref>PMID:8506384</ref> <ref>PMID:9472020</ref> [[http://www.uniprot.org/uniprot/IF2G_YEAST 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. [[http://www.uniprot.org/uniprot/EI2BA_YEAST 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.<ref>PMID:8506384</ref> <ref>PMID:9472020</ref> [[http://www.uniprot.org/uniprot/EI2BE_YEAST 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.<ref>PMID:8506384</ref> <ref>PMID:9472020</ref> [[http://www.uniprot.org/uniprot/EI2BG_YEAST 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.<ref>PMID:8506384</ref> <ref>PMID:9472020</ref> | + | [https://www.uniprot.org/uniprot/EI2BA_YEAST 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.<ref>PMID:8506384</ref> <ref>PMID:9472020</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Adomavicius, T]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Pavitt, G D]] | + | [[Category: Adomavicius T]] |
| - | [[Category: Roseman, A M]] | + | [[Category: Pavitt GD]] |
| - | [[Category: Translation]] | + | [[Category: Roseman AM]] |
| - | [[Category: Translational control eif2 phosphorylation integrated stress response eif2b translation]]
| + | |
| 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
Protein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates translational control at the ISR core. To provide insight into the mechanism of translational control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms bound with its nucleotide exchange factor eIF2B by electron cryomicroscopy. The structures reveal that eIF2 undergoes large rearrangements to promote binding of eIF2alpha to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2alphaP binding to eIF2B, suggesting that the higher affinity of eIF2alphaP for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex.
The structural basis of translational control by eIF2 phosphorylation.,Adomavicius T, Guaita M, Zhou Y, Jennings MD, Latif Z, Roseman AM, Pavitt GD Nat Commun. 2019 May 13;10(1):2136. doi: 10.1038/s41467-019-10167-3. PMID:31086188[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
- ↑ 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
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