PITTSBURGH--Carnegie Mellon University biologists are the first to show that minor changes in the tail of one protein cripple yeast's ability to assemble protein-making machines called ribosomes. The findings, published in a recent issue of Molecular Cell, ultimately could help scientists develop better drugs to fight fungal infections.

"Our findings are the first to link the structure of a ribosomal protein to a critical step in the pathway to assembling a fully functional ribosome," explained John Woolford, professor of biological sciences at the Mellon College of Science at Carnegie Mellon. "Understanding the molecular basis of ribosome assembly offers a rational scheme for designing drugs to interfere with that process."

A complex of protein and ribonucleic acid (RNA), ribosomes are present in vast quantities inside every cell. There, they translate genetic information into proteins that control many activities, including cell movement, metabolism, division and response to the environment. Because ribosomes are essential for protein production, problems with their assembly inevitably spell cell death.

Woolford found that changing the tail of a ribosomal protein called S14 prevented it from processing a chunk of RNA destined to become part of a mature ribosome. Drugs that target the tail of S14 would likely interfere with ribosome assembly, according to Woolford, who added that such agents would destroy an infectious fungus while leaving animal or plant cells unharmed.

Using processes known as transformation and gene disruption, Woolford's group engineered the yeast Saccharomyces cerevisiae, (common baker's yeast) to contain two genes for S14. One normal, or wild-type, gene instructed production of a fully functional S14 protein, while a mutant gene coded for the production of an S14 with an altered tail. After growing the yeast under normal conditions, Woolford turned off the wild-type gene and observed the consequences when only t
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Contact: Lauren Ward
wardle@andrew.cmu.edu
412-268-7761
Carnegie Mellon University
7-Jun-2004

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