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Translation initiation

Translation initiation is the rate-limiting step in protein synthesis and therefore most tightly controlled. The most prevalent mechanism in eukarya is the cap-dependent pathway where a crucial step is the loading of the 43S pre-initiation complex onto the 5’ end of the message and the following scanning process. This is accomplished by eIF4F that consists of eIF4E, the scaffold eIF4G and eIF4A, an ATP-dependent RNA helicase. mRNAs with long and highly structured 5 ´-untranslated regions, e.g. present in ODC or VEGF, are over-proportionally translated upon up-regulation of eIF4F, which is a potential target for the development of anti- cancer chemotherapeutics. 

Earlier we reported the structure of the complex formed by yeast eIF4G's middle domain and full-length eIF4A at 2.6-A resolution [1]. This structure allowed insights in the mechanism of eIF4A's activation by eIF4G. In the future our group is interested in the design of new - respectively the improvement of existing- compounds to inhibit this activity.

Related PDBs: 2VSO, 2VSX      

  1. Schütz, P., Bumann, M., Oberholzer, A. E., Bieniossek, C., Trachsel, H., Altmann, M., and Baumann, U. (2008) Crystal structure of the yeast eIF4A-eIF4G complex: an RNA-helicase controlled by protein-protein interactions. Proc. Natl. Acad. Sci. U.S.A. 105, 9564–9569
  2. Dominguez, D., Altmann, M., Benz, J., Baumann, U., and Trachsel, H. (1999) Interaction of translation initiation factor eIF4G with eIF4A in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 274, 26720–26726