NMR Spectroscopy of Translation Initiation Factors

Protein translation refers to the process of protein synthesis which is carried out at the ribosome. In the translation process, the information encoded in the transcribed mRNA is used to specify the sequence of amino acids of the new polypeptide chain. The level of protein synthesis requires fine-tuned modulation during normal cell growth as well as in response to environmental stress situations, whereas malfunctioning in its regulation is associated with tumorigenesis and cancer. In eukaryotes, the initiation of translation requires the interaction of a large number of initiation factors (eIF). The goal of the proposed research is to elucidate the interaction of the human translation initiation factors eIF5B and eIF4A on a structural basis employing NMR spectroscopy. In order to achieve this, we will overexpress the interacting domains in bacteria and solve the solution structure of the components individually as well as in their complexed form. The findings of these studies not only will lead to a more detailed understanding of the molecular mechanism of the initiation process but will also offer insights into the regulatory steps involved in translation in higher organism.