Yale scientists have crossed an important threshold in their effort to determine the positions of atoms in the ribosome--which will not only lead to an improved understanding of protein synthesis, but which could also have medical implications.
The Yale group has 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 so that its parts can be identified and positioned.
Many of the antibiotics used to fight bacterial infections operate by interfering with the function of their ribosomes. Continued research in this area could eventually lead to improving the effectiveness of antibiotics, according to the study's principal investigator, Thomas A. Steitz, Ph.D., Eugene Higgins Professor of Molecular Biophysics and Biochemistry at Yale.
"We're very excited to be on the brink of understanding this enormous macromolecular machine at the atomic level," said Steitz, whose study will appear in the August 26 issue of Nature. "With our ongoing research, there is reason to hope that the first atomic-resolution descriptions of the ribosome will appear in the near future."
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 also intriguing to those interested in enzymes--biological objects that enhance the rate of biochemical reaction.
Unlike almost all other enzymes, the ribosome is not a protein. Instead, it is an assembly of protein and RNA molecules that is about two thirds RNA. The structure now beginning to emerge is likely to illuminate both the chemical and evolutionary reasons why this is so.
"The human genome includes instructions for roughly 100,000 different proteins," said Steitz who collaborated on the study with Peter Moore, Ph.D., Eugene Higgins Professor of Chemistry at Yale. "The question we are still trying to answer is how the ribosome translates the genetic code into proteins on a molecular basis. The answer will lead to further understanding of early stages of evolution."
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 underway at Yale for four years, and it derives from work on ribosome crystallization that began in Germany and Russia over 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.
Other members of the research team included Yale postdoctoral fellows Nenad Ban, Poul Nissen and Jeffrey Hansen. Malcolm Capel of Brookhaven National Laboratory was also a member of the research team. The synchrotron used in the study was provided by Brookhaven National Laboratory and was essential for making accurate measurements of x-ray diffraction intensities.
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