Form follows function – Argonne’s Structural Biology Center reveals the ribosome’s structure

The atomic structure of one of the cell’s most important molecules — the ribosome — was pictured using Argonne’s Structural Biology Center (SBC).

The structure provides information on how the two-part ribosome — a large molecular machine found in all cells — forms proteins, the building blocks of organisms, by translating the information encoded in genes. Yale University researchers solved at unprecedented resolution the structure of the large 50S subunit that catalyzes the peptide bond. Two groups worked on the structure of the 30S subunit that binds messenger RNA. One is from Britain’s Medical Research Council Laboratory of Molecular Biology. The other group is from the Max Planck Institute in Germany and the Weizmann Institute in Israel.

The SBC provided detailed pictures of how ribosomes use amino acids as the raw material to manufacture proteins to the genes’ exact specifications. The work also showed previously unknown details of how antibiotics actually work.

These large structures are just a few of the more than 100 determined in 2000.

A WORLD-RENOWNED RESOURCE
Researchers from across the world rely on the SBC at Argonne’s Advanced Photon Source (APS). The nation’s most brilliant source of X-rays, the APS lets researchers at the SBC collect atomic-scale structural data faster than at any other biological research facility in the nation.

"The structure provides scientists with clues to the function of these biological molecules and will one day help doctors treat or cure diseases," said Structural Biology Center Director Andrzej Joachimiak.

The APS’s brilliant X-rays are shone onto tiny, frozen, protein crystals and captured by an electronic camera. Experts use computers to convert the data into three-dimensional images.

Argonne biologists at the SBC are also greatly reducing the time required to solve molecular structures. Using new tools and techniques developed here, research that recently took months or years now takes only hours or days.

Recent Argonne advances include the development of larger, faster X-ray detectors that provide information in greater detail and the robotic automation of the time-consuming laboratory processes for growing protein copies and crystals. For example, while manual methods only yield two to four protein clones a week, Argonne’s robotic facility can create up to 382 per week.

CENTER FOR STRUCTURAL GENOMICS
The Midwest Center for Structural Genomics is based at Argonne. Funded by the National Institute of General Medical Science, part of the National Institutes of Health, the Midwest center is composed of university research teams from the United States, Canada and Great Britain that work under Argonne leadership.

In 2000, the center contributed 15 structures to the Protein Data Bank, the international repository for the structures of proteins and other macromolecules.

The research center’s goal is to cut the average cost for determining the three-dimensional structures of proteins from $100,000 to $20,000, as well as to cut the time it takes to analyze a protein from months and years to days and hours. The group will also select protein targets from all three kingdoms of life — Eukarya, Archaea and Bacteria — with an emphasis on new protein folds and proteins from disease-causing organisms.

More information is available on the Internet. The SBC Web site is at www.sbc.anl.gov; the Midwest Center for Structural Genomics is at www.mcsg.anl.gov.

For more information please contact Evelyn Brown