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Albany 2001

category image Biomolecular
Stereodynamics
SUNY at Albany
June 19-23, 2001

Structure and Function in the Large Ribosomal Subunit

In 2000, an atomic resolution structure for the large subunit from Haloarcula marismortui was published that included 2833 of its 3045 nucleotides and 27 of its 31 proteins (1), and results reported on large subunit complexes with peptidyl transferase substrate and transition state analogs showed that the ribosome is a ribozyme (2). Refinement has now revealed the positions of more than two thousand water molecules and about two hundred cations that are stably associated with the subunit. The free-R factor of the structure is now close to 20%. The structure is stabilized by RNA/cation interactions, RNA/RNA interactions, and protein/RNA interactions. A new RNA/RNA interaction, called the "A-minor motif", stabilizes 23S rRNA tertiary structure in many places. The crosslinking of 23S rRNA sequences by the extended and highly basic tails of several ribosomal proteins also makes an important contribution. The binding sites of 6 ribosomal proteins include a novel RNA secondary structure motif called the "kink-turn". In addition, structures have been obtained for complexes of the large subunit with several new peptidyl transferase substrates and substrate analogs. The data indicate that these substrates react to form peptide bonds in the crystals under investigation. Finally, substantial progress has been made in our crystallographic study of the interactions of antibiotics with the large ribosomal subunit, many of which bind in the neighborhood of the peptidyl transferase site.

    Reference and Footnotes
  1. Ban et al. (2000), Science 289: 905-920.
  2. Nissen et al. (2000), Science 289: 920-930

J. Hansen (1), D. Klein (1), M. Schmeing (1), J. Ippolito (1), P. Nissen (1) , N. Ban (1)à , P.B. Moore (1,2) and T.A. Steitz (1,2,3).

(1) Dept. of Molecular Biophysics and Biochemistry, Yale University; (2) Department of Chemistry, Yale University, New Haven, CT 06520-8107; (3) Howard Hughes Medical Institute;
email: peter.moore@yale.edu
current addresses:   Dept. of Molec. and Struct. Biol., Aarhus University, Aarhus, DK-8000, Denmark. à Institute for Molec. Biol. and Biophys. ETHZ, ETH Honggerberg, CH-8093, Zurich, Switzerland.