This model grew out of Lancet's hunch that the olfactory system might function in a way similar to the immune system, which also needs to recognize a huge array of foreign molecules. To that end, the immune system produces a large set of antibodies capable of trapping different invaders.
Now, in a new study reported in the May issue of Protein Science, graduate student Yitzhak Pilpel and Lancet have provided new evidence showing how the "generalist" model works at the structural level. They have also shown that the similarity between olfactory receptors and antibodies may go even further than Lancet originally proposed.
By analyzing the DNA sequences of 200 olfactory receptors -- out of the estimated total of 500-1,000 in the olfactory system -- the scientists were able to model the receptors' 3-D structure. The results indicate that all olfactory receptors -- made up of some 300 amino acids -- have a similar structure: They contain large, framework-like regions that are shared by all members of this enormous family of recognition devices. It is only a small and well-defined region containing about 20 amino acids that varies greatly from one receptor to another. That's precisely the site where an odor molecule can fit like a key into a keyhole.
These results reveal the secret of smell in all its simplicity and elegance: The keyhole-sized region can easily be altered to accommodate a vast array of new odors while the "framework" of the receptor remains largely unchanged. This structural picture is very similar to what has long been known about antibody molecules: They contain a small, highly variable region geared to recognize an endless army of foreign invaders. Pilpel and Lancet believe they have uncovered the long-sought equivalent of the antibodies' "hypervariable" region in the receptors for odor molecules.
If the Institute model of olfactory receptors is supported by further studies,
it may prove useful for the developmen
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Contact: Jeffrey J. Sussman
Jeffrey@acwis.org
212-799-2500
American Committee for the Weizmann Institute of Science
29-Jun-1999