Structural studies on ribosomes. (360G-Wellcome-082086_Z_07_Z)

Following our determination of the atomic structure of the 30S subunit in 2000, we have recently solved the high resolution structure (2.8 ) of the entire ribosome complexed with its mRNA and tRNA ligands. We propose to determine the structures of the ribosome bound to several ligands and factors. These include release factors RF1 and RF2, which recognize stop codons and release the nascent polypeptide chain; ribosome recycling factor, which is involved in recycling ribosomes to start a new rou nd of translation; the endonuclease relE, which binds to stalled ribosomes and cleaves mRNA; and the complex of the protein SmpB and tmRNA, which is used by bacteria to rescue ribosomes stalled on defective mRNA. We also propose to crystallize complexes of the ribosome in complex with the GTPase factors EF-Tu and EF-G arrested at specific points along the translation pathway. Structures of these complexes will shed light on the mechanisms underlying translation, including the interaction of fac tors with the ribosome and conformational changes during translation. Finally, we shall solve the structures of the eukaryotic small ribosomal subunit in complex with several initiation factors to understand structural changes along the initiation pathway.