Structural studies on factor assisted protein folding and targeting

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In every organism, translation of the genetic code into functional proteins is performed on the ribosome, a macromolecular machine of more than 2.3 MDa. Since ribosomes play a central cole in cell viability, their activity is intensely regulated by a host of ancillary factors and represent a major target of natural antibiotics. The high-resolution structures of the small (30S) and large (50S) ribosome subunit, in the past few years have revolutionized our understanding of ribosome structure and function. In our group we are in the unique position of being able to prepare four different types of ribosome crystals: Thermus thermophilus 30S and 50S subunits, Deinococcus radiodurans and T. thermophilus 70S ribosome. The aim of this proposal is to utilise the ribosomes and ribosome crystals produced in our laboratory as a platform for the preparation and study of novel ribosomal complexes. Our goals include obtaining high-resolution structures of the ribosome in various functional states: (i) both pre- and post-translocation, (ii) pre-peptide bond formation, as well as (iii) in complex with various translational and regulatory factors. We predict that the results that will be obtained will increase our comprehension of the translational process and will be of potential use for the rational development of new antibiotics.