STRUCTURAL STUDIES OF THE TRANSLATING RIBOSOME

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The ribosome is the protein factory of the biological cell. It reads genetic information encoded in the nucleotide sequence of a messenger RNA strand, while synthesizing the corresponding polypeptide. The ribosome likely evolved in the ancient protocell on Earth and its structural core and essential enzymatic activities are universally conserved. Structural studies of the ribosome in its functional states are central in uncovering the molecular dynamics and chemistry of its functions, the chemistry of RNA and the evolution of life on the planet. Recently, we determined near-atomic crystal structures of release factor-bound ribosomal complexes captured at termination of translation. These structures provide the structural basis for stop codon recognition, peptidyl hydrolysis, coupling of decoding and hydrolysis, and principal aspects of the Genetic Code. Our immediate next goals are crystal structures of pre-, intermediate and post-termination complexes at the relevant resolution of chemical bonds. Also pressing are the determinations of crystal structures of a number of ribosomal states in translation, captured with pertinent tRNAs, mRNA, factors, substrate analogs and/or antibiotics. Together, these structures will provide ?molecular snapshots? of the processes of protein translation, and allow structure-based design of novel antibiotics combating microbial infections.