White: Structural Studies of the Prokaryotic Ribosome

The ribosome coordinates protein synthesis in all cells, and it has been the focus of intensive study worldwide since its discovery nearly 50 years ago. With a molecular mass of over two million Daltons and no internal symmetry, the ribosome represents a huge technological problem for structural biologists. However, recent images from X-ray crystallography and electron microscopy studies are now approaching 5Å resolution, and images at atomic resolution are on the horizon. The prokaryotic ribosome contains some 50 proteins and three large RNA molecules, and these form two subunits. The small or '30S' subunit binds and decodes messenger (m) RNA, and the large or '50S' subunit binds transfer (t) RNA and performs peptide bond synthesis. Our approach to studying the ribosome is to isolate individual proteins and protein-RNA complexes, and then to determine their high-resolution structures by X-ray crystallography, NMR spectroscopy, or both. These modules have proved to be invaluable for interpreting the lower- resolution images of the entire subunits, and they can also be incorporated into these images to eventually build the entire complex. Shown below are the crystal structures of ribosomal protein S4 and the L11-RNA complex that were recently completed and published.

   

Ribosomal protein S4-RNA interaction surface
EMBO J 17:4545-4558, 1998

Complex between RNA and ribosomal protein L11
Cell 97:491-502, 1999

The ribosome is also an extremely ancient ribonucleoprotein complex that may represent the bridge between modern life and an earlier form of life based on RNA. Therefore, the ribosomal proteins are extremely ancient and are rather well conserved from bacteria to man. Over 20 ribosomal protein structures have now been determined (11 by our group), and they all contain simple protein folding motifs, many of which can be recognized in more recently evolved complex proteins. As part of an emerging structural genomics effort at St. Jude, the Department of Structural Biology intends to solve the structures of all the remaining ribosomal proteins in the coming years. This effort will also be important to the general ribosome project.

 

Last update: April 2003