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PDBsum entry 4zgo
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References listed in PDB file
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Key reference
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Title
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Cdc123, A cell cycle regulator needed for eif2 assembly, Is an ATP-Grasp protein with unique features.
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Authors
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M.Panvert,
E.Dubiez,
L.Arnold,
J.Perez,
Y.Mechulam,
W.Seufert,
E.Schmitt.
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Ref.
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Structure, 2015,
23,
1596-1608.
[DOI no: ]
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PubMed id
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Abstract
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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 eIF2γ. 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 eIF2αγ 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 eIF2γ
to eIF2α.
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