Fertilization Protein Structure To AID in Leukemia Treatment

October 30, 1996

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 stages of their development. Because a CD38 molecule has a remarkable similarity to the cyclase protein, Stout and his collaborators think that CD38 molecules also pair up to create an internal cavity. However, unlike cyclase, CD38 has a tail reaching across the cell membrane, providing a means for it to transmit signals to the inside of white blood cells. "By modifying the chemical bonds in molecules outside the cell, the size and shape of the protein cavity may be changed, and this effect can be transmitted across the cell membrane by the attached tail," explains Kamal Shukla, program director in NSF's division of molecular and cellular biosciences, which funded Stout's research.

The Scripps researchers hope that drugs targeted toward the cavity in CD38 could be used to alter signal transmission and allow the immune system to eliminate leukemia cells.
-end-


National Science Foundation

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.