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BIOLOGICAL SCIENCES / BIOCHEMISTRY
Structure of an archaeal heterotrimeric initiation factor 2 reveals a nucleotide state between the GTP and the GDP states
Laboratoire de Biochimie, Ecole Polytechnique, Centre National de la Recherche Scientifique, F-91128 Palaiseau Cedex, France
Edited by V. Ramakrishnan, Medical Research Council, Cambridge, United Kingdom, and approved October 2, 2007 (received for review July 23, 2007)
Initiation of translation in eukaryotes and in archaea involves eukaryotic/archaeal initiation factor (e/aIF)1 and the heterotrimeric initiation factor e/aIF2. In its GTP-bound form, e/aIF2 provides the initiation complex with Met–tRNA
. After recognition of the start codon by initiator tRNA, e/aIF1 leaves the complex. Finally, e/aIF2, now in a GDP-bound form, loses affinity for Met–tRNA and dissociates from the ribosome. Here, we report a 3D structure of an aIF2 heterotrimer from the archeon Sulfolobus solfataricus obtained in the presence of GDP. Our report highlights how the two-switch regions involved in formation of the tRNA-binding site on subunit 
exchange conformational information with 
and β. The zinc-binding domain of β lies close to the guanine nucleotide and directly contacts the switch 1 region. As a result, switch 1 adopts a not yet described conformation. Moreover, unexpectedly for a GDP-bound state, switch 2 has the "ON" conformation. The stability of these conformations is accounted for by a ligand, most probably a phosphate ion, bound near the nucleotide binding site. The structure suggests that this GDP–inorganic phosphate (Pi) bound state of aIF2 may be proficient for tRNA binding. Recently, it has been proposed that dissociation of eIF2 from the initiation complex is closely coupled to that of Pi from eIF2 upon start codon recognition. The nucleotide state of aIF2 shown here is indicative of a similar mechanism in archaea. Finally, we consider the possibility that release of Pi takes place after e/aIF2 has been informed of e/aIF1 dissociation by e/aIF2β.
e/aIF2 | G protein | initiation of translation | tRNA | start codon
Author contributions: Y.M. and E.S. designed research; L.Y., Y.M., and E.S. performed research; L.Y., Y.M., S.B., and E.S. analyzed data; and L.Y., Y.M., S.B., and E.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 2QMU and 2QN6).
This article contains supporting information online at www.pnas.org/cgi/content/full/0706784104/DC1.
*To whom correspondence should be addressed. E-mail: emma{at}botrytis.polytechnique.fr
© 2007 by The National Academy of Sciences of the USA
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