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The Frankenstein ProteinAnd its medical uses |
By Vlad Tarko, Senior Editor, Sci-Tech News
11th of September 2006, 13:35 GMT
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According to molecular biology textbooks, a gene encodes the sequence of aminoacids that makes up a protein. But now, scientists have discovered an unusual protein that doesn't follow exactly the sequence encoded by the gene. In fact, some of the peptides (short sequences of aminoacids) are stitched together in reverse order. The protein, nicknamed the "Frankenstein protein" is found on the surface of leukemia cells.
The example of this protein shows that after a protein has been formed according to the plan encoded by the gene, there might still be some additional shuffling. This discovery might have implications for the development of peptide vaccines against cancer
and infectious diseases. This is because the organism's immune system recognizes the foreign cells by detecting the peptides on their surfaces. Similarly, the peptides present on the surface of a developing cancer alert the immune system, which permits the production of antigens from one single protein.
Edus Warren, at the Fred Hutchinson Cancer Research Center in Seattle, and his colleagues have found that once a protein is assembled, a specialized part of the cellular machinery, called a proteasome, can reverse the order of some of the peptides. Such 'protein surgery' has also been seen in plants and single-celled organisms but the new discovery shows that the phenomenon might be more common than previously thought.
"The proteasome can splice peptides together," says Warren. "Every once in a while, new peptide bonds will be created, not just destroyed."
The proteasomes can potentially create thousands of different configurations starting from the information contained in a single gene. This means, on one hand, that the potential diversity of peptides on the cell surfaces is much larger than previously thought and, on the other hand, that many more antigens could be produced from a single protein.
This could have tremendous consequences for vaccines development and cancer research. For example, Warren's colleagues at the Ludwig Institute for Cancer Research in Brussels, Belgium, are currently running clinical trials of an antigen-specific cancer vaccine. Because of the discovery of this new mechanism, the potential applicability of peptide vaccines is now increased, Warren says.
Scientists don't known yet whether all cells use their proteasomes to shuffle all types of proteins, or whether the mechanism is specific to the immune system. Warren thinks that the same mechanism could be present elsewhere. "There is no reason why cells could not have learned how to use this mechanism to their advantage. But I don't think that people have ever looked," he says.
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