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National Institute of Allergy and
Infectious Diseases (NIAID)
http://www.niaid.nih.gov

FOR IMMEDIATE RELEASE
Sunday, July 4, 2004

Media Contact:
Linda Joy
(301) 402-1663
niaidnews@niaid.nih.gov
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3-D Structure of Anthrax Toxin Complex Solved

Scientists have determined a three-dimensional (3-D) molecular image of how anthrax toxin enters human cells, giving scientists more potential targets for blocking the toxin, the lethal part of anthrax bacteria. The finding also points to a possible way to design anthrax toxin molecules that selectively attack tumor cells, as described in the journal Nature published online July 4. The study, funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, was led by Robert C. Liddington, Ph.D., of the Burnham Institute in La Jolla, CA.

“This elegant work provides important new leads for the development of novel antitoxins to protect people from anthrax, a dangerous and serious bioterror threat,” says NIAID Director Anthony S. Fauci, M.D. “It also leads us closer to therapies that could save lives late in the disease when large amounts of toxin are present and antibiotics are less effective.”

Using an intense X-ray beam to determine the position of atoms in a crystal form of the protein complex, a scientific team mapped the 3-D structure of one of the anthrax toxin’s proteins docked to a human anthrax toxin receptor. Anthrax toxin uses a protein known as protective antigen to gain entry into human or animal cells. The protective antigen protein can bind either of two different cell receptors: CMG2 and TEM8. In this study, scientists solved the puzzle of the molecular structure of the protective antigen protein and CMG2 bound together.

Previously, different groups of scientists in separate studies had determined the 3-D structures of the anthrax protective antigen protein and the CMG2 receptor—but only when unbound from each other. The structure of the protective antigen protein-CMG2 receptor complex offers a more precise, finely detailed snapshot of a crucial step in the intricate molecular choreography that ushers anthrax toxin into cells. This detailed, 3-D image provides researchers clearer targets for shutting down this process. For researchers working on anthrax antitoxins, the new 3-D image is like having a roadmap that connects two cities rather than having only separate maps of the two cities.

The newly revealed structure also points to a potential new tumor treatment using a genetically modified anthrax toxin, Dr. Liddington says. The TEM8 cell receptor is commonly found in cells lining the blood vessels of tumors. Although the structure of the TEM8 receptor has not been determined, scientists expect it to be similar to that of the CMG2 receptor. “Computer modeling could enable us to design a version of the anthrax toxin that binds only to TEM8 and not to CMG2,” he notes. Such a toxin would kill tumor cells while leaving ordinary cells unharmed.

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Reference: E Santelli et al. Crystal structure of a complex between anthrax toxin and its host cell receptor. Nature. DOI: 10.1038/nature02763


NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Last Updated July 04, 2004