View source for 6qg3


==Structure of eIF2B-eIF2 (phosphorylated at Ser51) complex (model B)==
<SX load='6qg3' size='340' side='right' viewer='molstar' caption='[[6qg3]], [[Resolution|resolution]] 9.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qg3]] 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=6QG3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QG3 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>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6qg0|6qg0]], [[6qg1|6qg1]], [[6qg2|6qg2]]</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]), GCD7, TIF222, YLR291C, L8003.17 ([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]), GCD2, TIF224, YGR083C ([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]), SUI2, TIF211, YJR007W, J1429 ([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]), SUI3, TIF212, YPL237W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=6qg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qg3 OCA], [http://pdbe.org/6qg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qg3 RCSB], [http://www.ebi.ac.uk/pdbsum/6qg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qg3 ProSAT]</span></td></tr>
</table>
== 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/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>  [[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/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/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/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/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>  
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== 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<ref>PMID:31201334</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6qg3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</SX>
[[Category: Baker's yeast]]
[[Category: Large Structures]]
[[Category: Gordiyenko, Y]]
[[Category: Llacer, J L]]
[[Category: Ramakrishnan, V]]
[[Category: Eif2]]
[[Category: Eif2 alpha]]
[[Category: Eif2b]]
[[Category: Gef]]
[[Category: Heat domain]]
[[Category: Initiation factor]]
[[Category: Integrated stress response]]
[[Category: Isr]]
[[Category: Phosphorylation]]
[[Category: Translation]]
[[Category: Trnai]]