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| <SX load='6k71' size='340' side='right' viewer='molstar' caption='[[6k71]], [[Resolution|resolution]] 4.30Å' scene=''> | | <SX load='6k71' size='340' side='right' viewer='molstar' caption='[[6k71]], [[Resolution|resolution]] 4.30Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6k71]] is a 13 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6jlw 6jlw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K71 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6K71 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6k71]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6jlw 6jlw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6K71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K71 FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF2B1, EIF2BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2B2, EIF2BB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2B3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2B4, EIF2BD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2B5, EIF2BE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2S1, EIF2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2S2, EIF2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF2S3, EIF2G ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 4.3Å</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=6k71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k71 OCA], [http://pdbe.org/6k71 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6k71 RCSB], [http://www.ebi.ac.uk/pdbsum/6k71 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6k71 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=6k71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k71 OCA], [https://pdbe.org/6k71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k71 RCSB], [https://www.ebi.ac.uk/pdbsum/6k71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k71 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
- | [[http://www.uniprot.org/uniprot/EI2BG_HUMAN EI2BG_HUMAN]] Juvenile or adult CACH syndrome;Congenital or early infantile CACH syndrome;Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/EI2BB_HUMAN EI2BB_HUMAN]] Cree leukoencephalopathy;Juvenile or adult CACH syndrome;Congenital or early infantile CACH syndrome;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/IF2G_HUMAN IF2G_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN]] Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/EI2BD_HUMAN EI2BD_HUMAN]] Juvenile or adult CACH syndrome;Congenital or early infantile CACH syndrome;Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/EI2BE_HUMAN EI2BE_HUMAN]] Defects in EIF2B5 are a cause of leukodystrophy with vanishing white matter (VWM) [MIM:[http://omim.org/entry/603896 603896]]. VWM is a leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.<ref>PMID:11704758</ref> <ref>PMID:12325082</ref> <ref>PMID:12707859</ref> <ref>PMID:15776425</ref> <ref>PMID:19158808</ref> <ref>PMID:21484434</ref> | + | [https://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN] Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/IF2A_HUMAN IF2A_HUMAN]] 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_HUMAN EI2BG_HUMAN]] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [[http://www.uniprot.org/uniprot/IF2B_HUMAN IF2B_HUMAN]] 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_HUMAN EI2BB_HUMAN]] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [[http://www.uniprot.org/uniprot/IF2G_HUMAN IF2G_HUMAN]] As a subunit of eukaryotic initiation factor 2 (eIF2), involved in the early steps of protein synthesis. In the presence of GTP, eIF2 forms a ternary complex with initiator tRNA Met-tRNAi and then recruits the 40S ribosomal complex, a step that determines the rate of protein translation. This step is followed by mRNA binding to form the 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B (By similarity). Along with its paralog on chromosome Y, may contribute to spermatogenesis up to the round spermatid stage (By similarity).[UniProtKB:Q9Z0N1] [[http://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN]] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [[http://www.uniprot.org/uniprot/EI2BD_HUMAN EI2BD_HUMAN]] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [[http://www.uniprot.org/uniprot/EI2BE_HUMAN EI2BE_HUMAN]] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. | + | [https://www.uniprot.org/uniprot/EI2BA_HUMAN EI2BA_HUMAN] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. |
- | <div style="background-color:#fffaf0;">
| + | |
- | == Publication Abstract from PubMed ==
| + | |
- | A core event in the integrated stress response, an adaptive pathway common to all eukaryotic cells in response to various stress stimuli, is the phosphorylation of eukaryotic translation initiation factor 2 (eIF2). Normally, unphosphorylated eIF2 transfers the methionylated initiator tRNA to the ribosome in a guanosine 5'-triphosphate-dependent manner. By contrast, phosphorylated eIF2 inhibits its specific guanine nucleotide exchange factor, eIF2B. To elucidate how the eIF2 phosphorylation status regulates the eIF2B activity, we determined cryo-electron microscopic and crystallographic structures of eIF2B in complex with unphosphorylated or phosphorylated eIF2. The unphosphorylated and phosphorylated forms of eIF2 bind to eIF2B in completely different manners: the nucleotide exchange-active and -inactive modes, respectively. These structures explain how phosphorylated eIF2 dominantly inhibits the nucleotide exchange activity of eIF2B.
| + | |
- | | + | |
- | Structural basis for eIF2B inhibition in integrated stress response.,Kashiwagi K, Yokoyama T, Nishimoto M, Takahashi M, Sakamoto A, Yonemochi M, Shirouzu M, Ito T Science. 2019 May 3;364(6439):495-499. doi: 10.1126/science.aaw4104. PMID:31048492<ref>PMID:31048492</ref>
| + | |
- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
- | </div>
| + | |
- | <div class="pdbe-citations 6k71" style="background-color:#fffaf0;"></div>
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| | | |
| ==See Also== | | ==See Also== |
| *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] | | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
- | == References == | |
- | <references/> | |
| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Ito, T]] | + | [[Category: Ito T]] |
- | [[Category: Kashiwagi, K]] | + | [[Category: Kashiwagi K]] |
- | [[Category: Yokoyama, T]] | + | [[Category: Yokoyama T]] |
- | [[Category: Translation]]
| + | |
- | [[Category: Translation initiation]]
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