Team locates anthrax-receptor protein.Scientists have identified the protein that enables the anthrax toxin to attach to cells and trigger disease. Meanwhile, other researchers have mapped the molecular structure of the toxin component that does most of the damage to cells.
The findings, slated for release in the Nov. 8 issue of NATURE, were unveiled this week as infections from letter-borne anthrax spores continue to crop up across the eastern United States.
In hosts such as people and livestock, the anthrax bacterium emerges from its protective spore and begins to grow. It releases the three components of its toxin--known as lethal factor lethal factor
A gene mutation or chromosomal structural change that when expressed causes death before sexual maturity. , edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts. factor, and protective antigen (PA)--which assemble on cell surfaces. First to attach is PA, which binds to a receptor protein receptor protein
An intracellular protein or protein fraction having a high specific affinity for binding agents known to stimulate cellular activity, such as a steroid hormone or cyclic AMP. on a cell. Next, PA is cleaved cleaved (klevd) split or separated, as by cutting. by an enzyme there. Then, the other two toxin components attach to PA and gain entry into the cell. Once inside, lethal factor triggers the biochemical cascade that leads to anthrax's symptoms, which are most dangerous when the spores have been inhaled.
Until now, the protein serving as PA's docking station on cells was a mystery. John A.T. Young, a geneticist ge·net·i·cist
A specialist in genetics.
a specialist in genetics.
geneticist at the University of Wisconsin-Madison “University of Wisconsin” redirects here. For other uses, see University of Wisconsin (disambiguation).
A public, land-grant institution, UW-Madison offers a wide spectrum of liberal arts studies, professional programs, and student activities. , and his colleagues searched for it by inducing mutations in hamster ovary ovary, ductless gland of the female in which the ova (female reproductive cells) are produced. In vertebrate animals the ovary also secretes the sex hormones estrogen and progesterone, which control the development of the sexual organs and the secondary sexual cells. The researchers then mixed these mutant cells with PA. They found 10 cell lines to which PA couldn't bind, suggesting that these cells' PA receptors were absent or had been altered.
Drawing from a genetic library, the researchers began adding genes back to one of the cell lines to see which genes might restore the cell's binding to PA. They found such a gene. It encodes a cell-surface protein that the scientists dubbed anthrax toxin receptor.
The team then determined the part of the receptor to which PA binds. When they added extra copies of this receptor fragment to a mixture of rodent cells and anthrax toxin, the copies "soaked up the toxin and prevented it from attaching to the cell surfaces," Young says. If a drug were tailored to occupy this receptor site, it might thwart the disease, he says.
In a separate study, scientists reveal the three-dimensional shape of lethal factor and the mechanism it uses to sever a protein in cells, an action that triggers the disease. Knowing lethal factor's molecular shape might now enable scientists to design compounds that can disable it, says study coauthor Philip C. Hanna, a microbiologist at the University of Michigan (body, education) University of Michigan - A large cosmopolitan university in the Midwest USA. Over 50000 students are enrolled at the University of Michigan's three campuses. The students come from 50 states and over 100 foreign countries. in Ann Arbor.
Earlier this year, researchers reported progress on two other potential antidotes to anthrax toxin (SN: 5/12/01, p. 296; SN: 10/6/01, p. 212). All these studies are examples of "extraordinary, elegant science," says Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "It's incumbent upon us to do as much as we can to translate that into something that would [benefit] the public health," he says.