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Originally published In Press as doi:10.1074/jbc.M111804200 on February 21, 2002

J. Biol. Chem., Vol. 277, Issue 19, 17057-17061, May 10, 2002
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Crystal Structure of the N-terminal Segment of Human Eukaryotic Translation Initiation Factor 2alpha *

M. Cristina NonatoDagger , Joanne Widom, and Jon Clardy§

From the Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301

Eukaryotic translation initiation factor 2alpha (eIF2alpha ) is a member of the eIF2 heterotrimeric complex that binds and delivers Met-tRNA<UP><SUB>i</SUB><SUP>Met</SUP></UP> to the 40 S ribosomal subunit in a GTP-dependent manner. Phosphorylation/dephosphorylation of eIF2alpha at Ser-51 is the major regulator of protein synthesis in eukaryotic cells. Here, we report the first structural analysis on eIF2, the three-dimensional structure of a 22-kDa N-terminal portion of human eIF2alpha by x-ray diffraction at 1.9 Å resolution. This structure contains two major domains. The N terminus is a beta -barrel with five antiparallel beta -strands in an oligonucleotide binding domain (OB domain) fold. The phosphorylation site (Ser-51) is on the loop connecting beta 3 and beta 4 in the OB domain. A helical domain follows the OB domain, and the first helix has extensive interactions, including a disulfide bridge, to fix its orientation with respect to the OB domain. The two domains meet along a negatively charged groove with highly conserved residues, indicating a likely site for protein-protein interaction.


* This work was supported by Grants CA59021 from the National Institutes of Health (to J. C.). Portions of this work were carried out at the Cornell High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation under award DMR-9311772, using the resources of the Macromolecular Diffraction Facility at CHESS (MacCHESS), which is supported by Grant RR-01646 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and the structure factors (code 1KL9) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

Dagger Supported by Fundação de Amparo a Pesquisa do Estado de São Paulo.

§ To whom correspondence should be addressed. Tel.: 607-255-6145; Fax: 607-255-1253; E-mail: jcc12@cornell.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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