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Fertilization Protein Structure To AID in Leukemia Treatment

The structure of a protein recently discovered by C. D. Stout at the Scripps Research Institute in La Jolla, California, is providing insights into the details of the interaction between sperm and egg. Remarkably, the same structure may hold a key to new treatments for leukemia, a kind of cancer that attacks the blood.

The research, supported by the National Science Foundation, has revealed a previously unknown relationship between a protein in the eggs of a marine mollusk and a protein on the outside of human white blood cells. The work is published in the November issue of Nature Structural Biology.

The egg protein is from the California sea snail, Aplysia californica, an animal used by biologists to study the process of fertilization. The details of the events that occur at the molecular level when a sperm cell joins with an egg are often the same throughout the animal kingdom, including in humans. One of the first events is that a flood of calcium ions is released as a signal to the egg to prepare to begin dividing. The flood of ions is controlled by a regulatory molecule, a sort of molecular switch, termed a secondary messenger.

The secondary messenger is synthesized inside the egg from the building blocks of DNA. The synthesis reaction requires a specialized protein, known as ADP ribosyl cyclase. It is this protein that has been studied by the researchers at Scripps. By preparing crystals of the protein and scattering x-rays off them, a three-dimensional image has been reconstructed. The image reveals that two of the molecules combine together to create a hole, or molecular cavity, between the proteins. Inside this cavity the protein traps the DNA building blocks and rearranges their pattern of chemical bonds to synthesize the messenger.

In leukemia, white blood cells have a signaling protein, called CD38, which in normal cells is only present in early
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Contact: Cheryl Dybas
cdybas@nsf.gov
703-306-1070
National Science Foundation
30-Oct-1996


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