Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features

Michel Panvert 1 Etienne Dubiez 1 Lea Arnold 2 Javier Perez 3 Yves Mechulam 1 Wolfgang Seufert 2 Emmanuelle Schmitt 1
1 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique
2 UR - Universität Regensburg
3 SSOLEIL - Synchrotron SOLEIL
Abstract : Eukaryotic 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 eIF2 gamma. The structures show that Cdc123 resembles enzymes of the ATP-grasp family. Indeed, Cdc123 binds ATP-Mg2+, and conserved residues contacting ATP-Mg2+ are essential for Cdc123 to support eIF2 assembly and cell viability. A docking of eIF2 alpha gamma 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 eIF2 gamma to eIF2 alpha.
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Structure, Elsevier (Cell Press), 2015, 23 (9), pp.1596-1608. 〈10.1016/j.str.2015.06.014〉
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Michel Panvert, Etienne Dubiez, Lea Arnold, Javier Perez, Yves Mechulam, et al.. Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features. Structure, Elsevier (Cell Press), 2015, 23 (9), pp.1596-1608. 〈10.1016/j.str.2015.06.014〉. 〈hal-01222821〉

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