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News

Three-dimensional structure of a protein that may open door to development of highly specific cell killer

Case Western Reserve University : 09 April, 2002  (Technical Article)
CWRU researchers have determined the three-dimensional structure of a protein that may open the door to the development of a highly specific cell killer and a new generation of antibiotics
CWRU researchers have determined the three-dimensional structure of a protein that may open the door to the development of a highly specific cell killer and a new generation of antibiotics

In Molecular Cell, Menachem Shoham, an associate professor in the School of Medicine's Department of Biochemistry, and his team described the structure and function of the colicin E3 protein. Colicins kill Escherichia coli by binding to a surface receptor of the bacteria, entering the cell and 'intoxicating' it.

The crystal structure of colicin E3 reveals a Y-shaped protein composed of three parts. The stem of the Y, which resembles a telephone cord, binds to E. coli bacteria. One arm of the Y is responsible for getting the molecule into the cell, while the other arm shuts down the ribosomes, the cell's protein assembly line, thereby killing the cell.

This finding provides insight into the action of a highly specific cell killer. The discovery opens the door for the development of new therapeutic agents to kill specific cells, such as cancer cells. This would require replacing the stem of the Y with a particular molecular part capable of recognizing a certain type of cancer cell. Another potential application could be the development of new antibiotics to kill harmful bacteria.

The cells producing colicin E3 have a mechanism for protection of their ribosomes. They are immune to the action of colicin E3 by virtue of an immunity protein. The study revealed how the immunity protein 'handcuffs' colicin E3 and renders it harmless. This discovery could be applied to kill cells in certain tissues and protect others.
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