5dbo

Crystal structure of the tetrameric eIF2B-beta2-delta2 complex from C. thermophilum

spinqualitylabelsall models 5dbo, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dbo is a 4 chain structure with sequence from Chaetomium thermophilum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0S811_CHATD Publication Abstract from PubMed Eukaryal translation initiation factor 2B (eIF2B) acts as guanine nucleotide exchange factor (GEF) for eIF2 and forms a central target for pathways regulating global protein synthesis. eIF2B consists of five non-identical subunits (alpha-), which assemble into a catalytic subcomplex (gamma, ) responsible for the GEF activity, and a regulatory subcomplex (alpha, beta, delta) which regulates the GEF activity under stress conditions. Here, we provide new structural and functional insight into the regulatory subcomplex of eIF2B (eIF2BRSC). We report the crystal structures of eIF2Bbeta and eIF2Bdelta from Chaetomium thermophilum as well as the crystal structure of their tetrameric eIF2B(betadelta)2 complex. Combined with mutational and biochemical data, we show that eIF2BRSC exists as a hexamer in solution, consisting of two eIF2Bbetadelta heterodimers and one eIF2Balpha2 homodimer, which is homologous to homohexameric ribose 1,5-bisphosphate isomerases. This homology is further substantiated by the finding that eIF2Balpha specifically binds AMP and GMP as ligands. Based on our data, we propose a model for eIF2BRSC and its interactions with eIF2 that is consistent with previous biochemical and genetic data and provides a framework to better understand eIF2B function, the molecular basis for Gcn-, Gcd- and VWM/CACH mutations and the evolutionary history of the eIF2B complex. Architecture of the eIF2B regulatory subcomplex and its implications for the regulation of guanine nucleotide exchange on eIF2.,Kuhle B, Eulig NK, Ficner R Nucleic Acids Res. 2015 Sep 17. pii: gkv930. PMID:26384431 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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