6caj
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Electron cryo-microscopy of the eukaryotic translation initiation factor 2B from Homo sapiens== |
| + | <StructureSection load='6caj' size='340' side='right' caption='[[6caj]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6caj]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CAJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CAJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C7B:2-(4-chloranylphenoxy)-~{N}-[4-[2-(4-chloranylphenoxy)ethanoylamino]cyclohexyl]ethanamide'>C7B</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6caj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6caj OCA], [http://pdbe.org/6caj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6caj RCSB], [http://www.ebi.ac.uk/pdbsum/6caj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6caj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[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/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> [[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/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/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. | ||
| + | == Function == | ||
| + | [[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/EI2BE_HUMAN EI2BE_HUMAN]] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [[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/EI2BG_HUMAN EI2BG_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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. | ||
| - | + | Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.,Tsai JC, Miller-Vedam LE, Anand AA, Jaishankar P, Nguyen HC, Renslo AR, Frost A, Walter P Science. 2018 Mar 30;359(6383). pii: 359/6383/eaaq0939. doi:, 10.1126/science.aaq0939. PMID:29599213<ref>PMID:29599213</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6caj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Anand, A A]] | ||
| + | [[Category: Frost, A]] | ||
| + | [[Category: Jaishankar, P]] | ||
| + | [[Category: Miller-Vedam, L E]] | ||
| + | [[Category: Nguyen, H C]] | ||
| + | [[Category: Renslo, A R]] | ||
| + | [[Category: Tsai, J C]] | ||
| + | [[Category: Walter, P]] | ||
| + | [[Category: Decameric complex]] | ||
| + | [[Category: Guanine nucleotide exchange factor]] | ||
| + | [[Category: Isrib-bound]] | ||
| + | [[Category: Translation]] | ||
| + | [[Category: Translation initiation]] | ||
Revision as of 13:52, 11 April 2018
Electron cryo-microscopy of the eukaryotic translation initiation factor 2B from Homo sapiens
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