The peptide chain in scorpion venom can cure excretory diseases

Scientists have recently discovered a chain of peptides found in scorpion venom that holds secrets to understanding and controlling cystic fibrosis and other secretory diseases.

On the December 28, 2007 issue of the Journal of Biological Chemistry , a team of international researchers described how this unusual peptide called GaTx1 controls the movement of ions and water outside the cell. planing by interacting with an important chloride tube. The research was funded by the National Institutes of Health, the National Science Foundation, and the Fiber Foundation.

Nael A. McCarty, an assistant professor at the Georgia Institute of Technology, explains: 'Toxins in scorpion venom, snakes, snails and spiders cause prey to be paralyzed by inhibiting nerve or tube activity. ions in the muscle make the prey unable to escape. These toxins are extremely useful in the study of potassium, calcium, and sodium tubes that they interact with. But this is the first poison discovered to be combined and selectively inhibited in two dimensions a known homogeneous chloride molecule '.

On the image is the poison GaTx1 in the form of a prominent ribbon on its hinge chain volume.GaTx1 can control the movement of ions and water outside the cell by interacting with an important chloride tube that patients with cystic fibrosis do not have.(Photo: Christopher Thompson)

Chloride tubes are very important in the process of excretion in many epithelial cells. But we only know very little about its structure and mechanism. Researchers know that when the chloride tube opens, it allows millions of chloride ions to enter and escape out of the epithelium. This flow creates osmotic gradient that helps water flow through.

More than 70,000 people worldwide suffer from cystic fibrosis. Lack of water in the air duct cells forms an unusually thick and sticky mucus that causes blockage, obstructing the airways and glands. Lack of water originates from the problem in the chloride tube called the cystic conductive conductive protein (CFTR).

In patients with cystic fibrosis, CFTR protein is mutated (often losing 1 amino acid or more); The result is a twisted protein structure. Most of the most common CFTR mutations lead to cystic fibrosis. At the point of losing amino acids, the chaperone protein is responsible for quality assurance in cells. Protein chaperone will combine with twisted-protein proteins and remove them from the cell. CFTR protein deficiency prevents water from circulating through the cell; thereby changing the condition in the air duct causing cystic fibrosis.

For other diseases, CFTR tubes are too functional to cause illness. Including diarrheal disease (a global concern that causes thousands of deaths every year), diarrhea of ​​intestinal inflammatory disease, dominant polycystic kidney disease, the fourth most serious disease in the United States is kidney disease the end.

Together with collaborators from the Hungarian Academy of Sciences, Emory University and the University of Calgary, scientists used high-performance liquid chromatography to extract the GaTx1 peptide chain from the venom of the giant Israeli scorpion. (Leiurus quinquestriatus hebraeus).

Julia Kubanek - associate professor at Georgia University of Biotechnology and University of Biochemistry - explains: 'We chose this technique because each peptide chain has water solubility as well as different hydrophilic properties. help them decay. "

Former Emory graduate student Matthew Fuller, along with graduate student at Georgia Tech University, Christopher Thompson, collected individual peptide chains separated by the HPLC system and then inserted each of the chloride tubes. sequence to determine which peptide chain is responsible for the overall effect of the venom. They discovered a strange peptide chain that binds to the CFTR protein, weighing about 3.7 kilodaltons. They call it GaTx1.

The researchers plan to use GaTx1 as a molecular probe to learn more about how chloride tubes are constituted and controlled. They also plan to study how this peptide molecule is useful in treating secretory diseases. According to McCarty, for people with diseases like diarrhea, GaTx1 can be used to prevent tubes from opening; thereby reducing diarrhea, often causing death in cholera patients or other diarrheal diseases.

To treat patients with cystic fibrosis, GaTx1 can be used to increase the amount of water by binding to chaperone protein binding points on the chloride tube. By inhibiting combination chaperone, CFTR protein will not be eliminated. The ions and water will circulate in the cell, thinning the mucus in the air duct.

McCarty said: 'Although the tubes will be twisted with twisting structure and only capable of operating 50%, chloride ions and water will be transported through the cell. This method is better than leaving chaperone protein to remove all CFTR proteins'.

McCarty studied CFTR throughout his career. Although he currently holds the position of a new assistant professor of pediatrics and a cystic fibrosis scientist at Emory University, he will continue his previous work in collaboration with researchers. at Georgia University of Technology.

McCarty added: ' GaTx1 can be used as a medicine for patients with cystic fibrosis and excretory diseases . My new role at Emory allows me to conduct studies that begin to explore drug treatment options for this poison. '