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

e the possibility that N-terminal acetylation plays an important role in the function of a large number of proteins in the cell," said first author, Daniel Scott, Ph.D. a scientist in Schulman's laboratory.

The pocket where N-terminally acetylated proteins bind may also be a good target for small molecules designed to block protein interactions that lead to many diseases, including cancers, Schulman said.

Schulman and her colleagues discovered the pivotal role N-terminal acetylation plays while studying interactions between the proteins Ubc12 and Dcn1. Other researchers have identified human Dcn1 as an oncogene that promotes some squamous cell head, neck and lung cancers.

The focus of the current study was the role the enzymes played in regulating activity of another complex, known as cullin-RING. The cullin-RING complex is the command center of a tagging system that cells use to modify a protein's function or to mark a protein for degradation. The cullin-RING targeted proteins include those that control such important biological processes as cell division and the immune response.

Dcn1 is bound to the cullin protein. In previous studies, Schulman and her colleagues showed that in yeast the Ubc12 and Dcn1 interaction led Ubc12 to transfer its cargo, a protein called NEDD8, to cullin. That step dramatically accelerated the activity of cullin-RING.

But a major question was how human Dcn1 and Ubc12 interact. The breakthrough came when the researchers realized that Ubc12 is among the 35 to 50 percent of proteins in which methionine is the amino acid involved in N-terminal acetylation. The investigators used a variety of laboratory techniques to demonstrate that the acetylated methionine of Ubc12 was essential to the Ubc12-Dcn1 interaction. Evidence included an X-ray image that shows Ubc12's acetyl-methionine buried in a pocket on the surface of Dcn1.

"The size and shape of the pocket indicate it might be a completely
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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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