6o9z
From Proteopedia
Electron cryo-microscopy of the eukaryotic translation initiation factor 2B bound to eukaryotic translation initiation factor 2 from Homo sapiens
Structural highlights
DiseaseEI2BD_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. FunctionEI2BD_HUMAN Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. Publication Abstract from PubMedThe integrated stress response (ISR) tunes the rate of protein synthesis. Control is exerted by phosphorylation of the general translation initiation factor eIF2. eIF2 is a guanosine triphosphatase that becomes activated by eIF2B, a two-fold symmetric and heterodecameric complex that functions as eIF2's dedicated nucleotide exchange factor. Phosphorylation converts eIF2 from a substrate into an inhibitor of eIF2B. We report cryo-electron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state. The structures reveal that the eIF2B decamer is a static platform upon which one or two flexible eIF2 trimers bind and align with eIF2B's bipartite catalytic centers to catalyze nucleotide exchange. Phosphorylation refolds eIF2alpha, allowing it to contact eIF2B at a different interface and, we surmise, thereby sequestering it into a nonproductive complex. eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response.,Kenner LR, Anand AA, Nguyen HC, Myasnikov AG, Klose CJ, McGeever LA, Tsai JC, Miller-Vedam LE, Walter P, Frost A Science. 2019 May 3;364(6439):491-495. doi: 10.1126/science.aaw2922. PMID:31048491[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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