Ribosome Structure, Chemistry Nobel Prize 2009

Ribosomal Crystalline Structure Analysis Explains Protein Activities

Oct 9, 2009

The crystalline structure of ribosomes has been studied by three scientific groups and the group leaders have received the 2009 Nobel Prize for explaining ribosomes.

In scientific inquiries, some questions are answered quickly, other inquiries may take decades or more. The X-ray crystallography of DNA by Watson, Crick, and Wilkins only took a few years. The work described here for ribosome structure took almost three decades – it was worth the investment. Drs. Ramakrishnan, Steitz and Yonath made major contributions to ribosome crystallography and used high-resolution functional ribosome complexes to unravel mysteries of protein synthesis. Basic science and medicine benefit immensely from these findings. Read the story that revealed details of ribosome structure.

These 3 senior scientists and lab directors each shared the chemistry prize for 2009:

The ribosome's overall basic, simple structure and functions are well-known. There are 70S ribosomes common to prokaryotes and mitochondria and chloroplasts, and 80S ribosomes common to eukaryotes. Ribosomes assist exclusively in protein synthesis.

In 1980, Ada Yonath generated the first three-dimensional crystals of a ribosome’s large subunit, and 20 years later Yonath generated ribosome images to determine each atom’s location. Yonath stabilized crystals by freezing them (liquid nitrogen at -196 °C) and she crystallized ribosomes from other resilient micro-organisms.

Yonath's X-ray crystallography yielded a 3-D ribosome picture of the very stable ribosomes from Geobacillus stearothermophilus, a hot-spring inhabitant, able to survive temperatures up to 75 C. Later Yonath studied ribosomes from the salt-loving Haloarcula marismortui from the Dead Sea. These ribosomes also are very stable, form good crystals and helped locate each atom in the X-ray crystal. Eventually, it was realized that the ribosome’s atomic structure could be mapped, and more scientists joined in the race to determine this - especially, Thomas Steitz and Venkatraman Ramakrishnan.

Molecular Insights into Ribosomes X-Ray Diffraction Studies of Protein/RNA Complexes

Every ribosome has two subunits, 1 small and 1 large. In humans, the small, ribosome unit has 1 large RNA molecule and about 32 proteins; the large subunit has 3 RNA molecules, and about 46 proteins. Each subunit has thousands of nucleotides and amino acids, with hundreds of thousands of atoms. In ribosomal, X-ray diffraction there are millions of atoms to see and study.

In the early 1990s, Yonath’s crystals had clear patterns of black dots, helpful for determining atomic locations, but lacking necessary phase angles for each atom in the X-ray crystallography. Soaking the crystal in mercury, tagged the ribosome's surface and permitted comparisons of the crystalline dotted patterns, with and without heavy atoms. Because ribosomes are so large, too many heavy atoms attached to the ribosome, and it was difficult to immediately determine the phase angles.

Steitz used ribosome images, prepared by the electron microscopist, Joachim Frank, to determine phase angles. Using information from heavy atoms, the phase angle was determined. In 1998, after about 20 years of work, Steitz published the first crystal structure of the ribosome’s large subunit with a resolution of 9 Ångström (1 Ångström = diameter of a hydrogen atom). Individual atoms were not visible, but long RNA molecules were revealed when the phase problem was solved, and improved crystals and more data, clarified the ribosomal image.

These 2009 Nobel Chemistry Laureates each published, in the year 2000, the final crystalline ribosomal structures with resolutions that allowed interpretation of atomic locations. Steitz imaged the large ribosomal subunit of Haloarcula marismortui. Yonath and Ramakrishnan obtained the structure of the small subunit from Thermus thermophilus. Thus, it was possible to map ribosome functionality at the most basic, atomic level.

Lodish, H. et al. 2000. Molecular Cell Biology. Fourth Ed., W. H. Freeman and Co., New York, N.Y.

The copyright of the article Ribosome Structure, Chemistry Nobel Prize 2009 in Scientific Inquiry is owned by Donald Reinhardt. Permission to republish Ribosome Structure, Chemistry Nobel Prize 2009 in print or online must be granted by the author in writing.