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Structure Cdc123 complexed with the C-terminal domain of eIF2gammaStructure Cdc123 complexed with the C-terminal domain of eIF2gamma
Structural highlights
Function[CD123_SCHPO] Regulates the cell cycle in a nutrient dependent manner. [IF2G_YEAST] 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. Publication Abstract from PubMedEukaryotic initiation factor 2 (eIF2), a heterotrimeric guanosine triphosphatase, has a central role in protein biosynthesis by supplying methionylated initiator tRNA to the ribosomal translation initiation complex and by serving as a target for translational control in response to stress. Recent work identified a novel step indispensable for eIF2 function: assembly of eIF2 from its three subunits by the cell proliferation protein Cdc123. We report the first crystal structure of a Cdc123 representative, that from Schizosaccharomyces pombe, both isolated and bound to domain III of Saccharomyces cerevisiae eIF2gamma. The structures show that Cdc123 resembles enzymes of the ATP-grasp family. Indeed, Cdc123 binds ATP-Mg(2+), and conserved residues contacting ATP-Mg(2+) are essential for Cdc123 to support eIF2 assembly and cell viability. A docking of eIF2alphagamma onto Cdc123, combined with genetic and biochemical experiments, allows us to propose a model explaining how Cdc123 participates in the biogenesis of eIF2 through facilitating assembly of eIF2gamma to eIF2alpha. Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features.,Panvert M, Dubiez E, Arnold L, Perez J, Mechulam Y, Seufert W, Schmitt E Structure. 2015 Sep 1;23(9):1596-608. doi: 10.1016/j.str.2015.06.014. Epub 2015, Jul 23. PMID:26211610[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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