Protein synthesis and degradation are tightly controlled key events in all living cells. Translation initiation is one of the stages where the rate of synthesis can be influenced. In the cap-dependent initiation a set of about 12 eukaryotic translation initiation factors ensures the fidelity of the assembly of an elongation-competent 80S ribosome on the proper start codon. The ternary complex eIF4F, which consists of the cap-binding protein eIF4E, the DEAD-box RNA-helicase eIF4A and the scaffold protein eIF4G, is a central player and responsible for recruitment of the 43S pre-initiation complex to the 5’ end of the mRNA as well as for the subsequent scanning process. Protein-protein interactions are crucial for the fidelity and rate of translation initiation and their atomic details should be elucidated. The interaction between eIF4G and eIF4A is essential for RNA-helicase stimulation. The demand for helicase activity is very pronounced in the translation of messages with long and structured 5’-untranslated regions, as they occur in the majority of growth- and proliferation related mRNAs. Unregulated protein synthesis during tumorigenesis is therefore linked to upregulation of eIF4F. Hence disruption of the eIF4A-eIF4G interface should be a worthwhile approach for developing new drugs. Intracellular protein degradation is performed by large proteolytic assemblies (AAA+ proteases), which denature and digest their substrates under ATP consumption. Here, the chemical energy stored in ATP is transformed via conformational rearrangements into a mechanical force that is used for substrate unfolding and translocation. Closer understanding of their mode of action is currently hampered by the lack of information on their 3D structures. Specific aims of this research project are: (i) characterization of protein-protein interaction surfaces in eIFs; (ii) determination of the eiF4G-controled conformational changes and the helicase mechanism of eIF4A; (iii) development of small molecules that are able to disrupt eIF4A-eIF4G complex formation; (iv) elucidation of the conformational changes occurring during the ATPase cycle of AAA+ proteases, especially of the essential metalloprotease FtsH.We employ X-ray crystallography, site-directed mutagenesis and spectroscopic methods in order to derive structure-function relationships.Expected results are more detailed pictures of protein-protein interaction surfaces that are of general interest for virtually all processes in a cell. Crystal structures of RNA-helicases and AAA+ proteases in different nucleotide-dependent conformations will greatly advance our understanding on how these molecules function.