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Molecule serves as a key in some protein interactions
Date:11/4/2011

Research led by St. Jude Children's Research Hospital scientists has identified an unexpected mechanism facilitating some protein interactions that are the workhorses of cells and, in the process, identified a potential new cancer drug development target.

The discovery involves a chemical known as an acetyl group. An estimated 85 percent of human proteins have this chemical added to the amino acid at one end of the protein. The addition comes in a process known as N-terminal acetylation. N-terminal acetylation occurs shortly after proteins are assembled. Although it has long been known that proteins are N-terminally acetylated, until now it was unknown how such acetylation could serve specific functions.

The findings came from scientists studying a system cells use to regulate the fate and function of proteins. The researchers showed that much like a key must fit precisely to work a lock, the acetylated end of one enzyme fits perfectly into a deep pocket on the surface of another protein. The connection helps accelerate the activity of a protein complex that is involved in regulating cell division and that has been linked to cancer. The research appears in the November 4 print edition of the journal Science.

The findings have potential implications for drug discovery and for understanding basic mechanisms governing the interaction of possibly thousands of proteins, said the study's senior author, Brenda Schulman, Ph.D., a member of the St. Jude Department of Structural Biology and a Howard Hughes Medical Institute investigator.

"The work presents a major new concept in protein-protein interactions," she said. "This raises the question of whether similar 'keys' on thousands of different proteins also unlock doors to allow them to function."

The research offers the first view of how N-terminal acetylation mediates protein interactions, bringing proteins together to do the work of cells. "These findings rais
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert  

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