Travel and Contact  Staff Only  Site Map  Help?     EMBL Hamburg > Courses and Conferences   Invitation   Poster   Speakers   Sponsors   Organisers   Programme   Pictures      16 September      15 September      PDB Exhibition   Ada Yonath - Ada Yonath and Ilana Agmon Structural Biol. Weizmann Inst. Rehovot, and Max-Planck Res. Unit, Hamburg Ribosomes, the universal cellular organelles catalyzing the genetic code translation into proteins, are protein/RNA assemblies built of two subunits. The small subunit is involved in initiating the process and controlling its fidelity. The large subunit creates the peptide bonds, ensures smooth aminoacids polymerization, and provides the path for emerging proteins. Crystal structures of ribosomal subunits complexes with substrate analogs, antibiotics and inhibitors confirmed that ribosomes provide positional, rather than chemical catalysis to its three tasks: peptide bond formation, aminoacid polymerization and peptidyl release. They also show that precise placement of the tRNAs, dominated mainly by remote interactions, is crucial for amino acid polymerization. By exploiting the conformational mobility of elements within the peptidyl transferase center (PTC) nucleotides, less well-placed reactants can be repositioned. One of these elements is a nucleotides playing a key role in D-aminoacid discrimination and antibiotics synergism. A sizable symmetry-related region in and around the PTC was revealed in all known large subunit’s structures. The unique ribosomal architecture, linked with the tRNA positioning, suggest that the mRNA/tRNA translocation shift occurs in conjunction with a rotatory motion of the universal single stranded aminoacylated tRNA-3’end. Guided along a structural pattern formed by ribosomal nucleotides, this motion results in stereochemistry suitable for peptide bond formation. The sole requirement for this mechanism is the accommodation of the initiator P-site tRNA in the PTC at its functional orientation. The rotatory motion is the major component of unified machinery for peptide bond formation, translocation and nascent protein progression. Its spiral nature ensures the entrance of the nascent peptide into the ribosomal exit tunnel. This tunnel provides a major antibiotics-binding pocket, and although it was assumed to be a passive path for the growing chains, it was found to possess dynamic properties facilitating gating and discrimination of nascent proteins, thus providing the mechanism for ribosomal involvement in cellular regulation.