View source for 6i3m


==eIF2B:eIF2 complex, phosphorylated on eIF2 alpha serine 52.==
<SX load='6i3m' size='340' side='right' viewer='molstar' caption='[[6i3m]], [[Resolution|resolution]] 3.93&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.93&#8491;</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'>[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>
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== Function ==
[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> 
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== 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<ref>PMID:31086188</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 6i3m" style="background-color:#fffaf0;"></div>

==See Also==
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Adomavicius T]]
[[Category: Pavitt GD]]
[[Category: Roseman AM]]