In the ribosome, clues to better antibiotics

Yale scientists have produced three-dimensional images of the largest component of the ribosome — the cellular structure responsible for synthesizing protein molecules in all organisms — at a resolution high enough that its parts can be identified and positioned.

Many of the antibiotics used to fight bacterial infections operate by interfering with the function of the bacterium’s ribosomes. Continued research in this area could eventually lead to improvements in the effectiveness of antibiotics, according to the study’s principal investigator, Thomas A. Steitz, Ph.D., the Eugene Higgins Professor of Molecular Biophysics and Biochemistry. Steitz collaborated on the study, which appeared in the Aug. 26 issue of Nature, with Peter Moore, Ph.D., the Eugene Higgins Professor of Chemistry.

Structural biologists have long viewed the ribosome as one of their field’s preeminent challenges, both because of its intrinsic biological importance and because of its large size and complexity. The ribosome is intriguing also to those interested in enzymes, organic catalysts that enhance the rate of biochemical reaction.

The research team used X-ray crystallography to obtain an image of the large ribosomal subunit from the bacterium Haloarcula marismortui that has a resolution of 5 angstroms. At that resolution, many of the structure’s proteins and RNA can be visualized.

The team’s advance culminates a project under way at Yale for four years, and it derives from work on ribosome crystallization that began in Germany and Russia more than 20 years ago. Since the Yale research team’s publication of an initial announcement of a lower-resolution structure last year, several other groups have begun making significant progress on other ribosomal components.