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J. Biol. Chem., Vol. 277, Issue 19, 17057-17061, May 10, 2002
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From the Department of Chemistry and Chemical Biology, Baker
Laboratory, Cornell University, Ithaca, New York 14853-1301
Eukaryotic translation initiation factor 2 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/).
Crystal Structure of the N-terminal Segment of Human Eukaryotic
Translation Initiation Factor 2
*
,
(eIF2
) is a member of the eIF2 heterotrimeric complex that binds and
delivers Met-tRNA
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 eIF2
by x-ray diffraction at 1.9 Å resolution. This structure contains two major domains. The N
terminus is a
-barrel with five antiparallel
-strands in an
oligonucleotide binding domain (OB domain) fold. The phosphorylation
site (Ser-51) is on the loop connecting
3 and
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.
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.
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