The x-ray crystal structure of wheat translation initiation factor eIF4E

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Date

2002

Authors

Sadow, Jennifer Beth Hurley

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Abstract

Proteins are the molecules that serve as the machinery of living organisms. The genetic code of life, stored in DNA, is transcribed to messenger RNA, which is exported from the nucleus to the cytoplasm of the cell. There, in the translation process, proteins and ribosomes assemble to form the active complex that synthesizes proteins from the mRNA template. Eukaryotic translation initiation factor 4E, or eIF4E, is a small protein that recognizes the “cap” structure at the 5’ end of mRNA. The binding of the cap by eIF4E and the association of eIF4E with the protein eIF4G allow translation to begin. Solving the three-dimensional structure of a protein gives valuable insight into its function. The mechanism of its activity can often be deduced from the structure, which can be used to find possible targets for chemical intervention. Because eIF4E is essential for translation, knowledge of its structure is important and could lead to commercial uses: an inhibitor which affected the cap-binding function of eIF4E would be a powerful herbicide. Here, the solved X-ray crystal structure of wheat eIF4E at 1.85 Angstroms is presented. As seen in the structures of other eIF4Es, the monomeric unit consists of an eight-stranded beta sheet, three alpha helices, and three large loop regions. Two of these loops contain tryptophans which have been observed, in previous structures, holding the cap in an aromatic stacking interaction. However, crystallized wheat eIF4E does not contain a bound cap molecule, despite having been co-purified with a cap analogue. Instead, two molecules of eIF4E form a dimer, the interface of which is formed by a beta sheet created from the loop regions of the monomer. Each molecule inserts one tryptophan into a hydrophobic pocket on the surface of the other molecule; this pocket is analogous to the cap-binding slot. The wheat eIF4E structure contains an unusual disulfide bridge, found in each monomer, that may hold the structure in an “open” conformation. This would force an opening between the cap-binding tryptophans, allowing for release of the cap, as well as the dimerization of eIF4E molecules which was observed in this X-ray structure.

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