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Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features
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.
Cited literature [57 references]
https://hal-polytechnique.archives-ouvertes.fr/hal-01222821
Contributor : Denis Roura <>
Submitted on : Friday, October 30, 2015 - 5:34:15 PM
Last modification on : Thursday, July 1, 2021 - 4:41:35 PM
Long-term archiving on: : Friday, April 28, 2017 - 8:03:40 AM
Contributor : Denis Roura <>
Submitted on : Friday, October 30, 2015 - 5:34:15 PM
Last modification on : Thursday, July 1, 2021 - 4:41:35 PM
Long-term archiving on: : Friday, April 28, 2017 - 8:03:40 AM
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STRUCTURE-D-15-00174.pdf
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