Molecular Structure of a Ribosome Revealed

Ribosomes make the stuff of life. They are the factories in every organism from bacteria to humans that manufacture enzymes, hormones, antibodies, and all other proteins. Like factory assembly lines, ribosomes are complex machines with many moving parts. Both the structure and function of ribosomes rely on a type of genetic material called RNA, for ribonucleic acid. Some bacterial ribosomes, for example, are composed of three strands of ribosomal RNA and more than 50 different proteins arranged in two major subunits.

Like any production plant, ribosomes require blueprints and raw materials. These blueprints are strands of messenger RNA, each of which carries the genetic sequence of a specific protein. The raw materials are amino acids, the building blocks of proteins, which are carried to the ribosome by transfer RNA. Nowhere else in the cell do so many different types of genetic material and proteins interact.

The first structural snapshot of an entire bacterial ribosome. The structure, which is the largest determined by X-ray crystallography, may help researchers design new antibiotic drugs or optimize existing ones. The data was collected using the Advanced Light Source at Lawrence Berkeley National Laboratory.

Because each ribosome is so large and complex, researchers have been unable to completely understand how its many components work together as a biological machine. For more than 30 years, they have tried to access the ribosome's molecular secrets by deciphering its three-dimensional structure so they could study it in detail.

Now, in a technical tour de force, Dr. Harry Noller and his coworkers at the University of California, Santa Cruz have used a technique called X-ray crystallography to obtain the first structure of a complete bacterial ribosome. In this technique, scientists bombard a tiny crystal of the molecule under study with high-energy X-rays, then piece together the molecule's shape by tracing the directions in which the energy is scattered. Knowing what a molecule looks like can say a lot about how it works.

The ribosome structure, although it is not detailed enough to reveal the location of individual atoms, does show the researchers how various parts of the ribosome fit together, how it positions its raw materials, and where the protein is assembled inside the whole complex. This bacterial ribosome is the largest asymmetric molecular structure ever determined by X-ray crystallography. (Some equally large virus structures have been obtained, but the symmetry of these structures greatly simplifies the process.) Now that the technique has been worked out, researchers expect a more detailed picture of the ribosome--one in which they can pinpoint every atom--within a year.

In addition to providing invaluable insights into a critical cellular component, the new images may lead to clinical applications. Many of today's antibiotics work by interfering with the function of ribosomes in harmful bacteria. A more detailed knowledge of these biological machines may help scientists develop new antibiotic drugs or improve existing ones.

REFERENCES

Cate JH, Yusupov MM, Yusupova GZ, Earnest TN, Noller HF. X-ray Crystal Structures of 70S Ribosome Functional Complexes. Science 1999;285:2095-104.

Culver GM, Cate JH, Yusupova GZ, Yusupov MM, Noller HF. Identification of an RNA-Protein Bridge Spanning the Ribosomal Subunit Interface. Science 1999;285:2133-5.

Reporters may call Alisa Zapp Machalek at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Cell Biology and Biophysics who can comment on this work.