Researchers image crucial anthrax protein
(麻豆淫院Org.com) -- Anthrax, long feared for its potential as a biological weapon, has lost some of its mystery. Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory, in collaboration with scientists at the University of Chicago, have determined the structure of a protein crucial to the virulence of anthrax bacteria.
One of anthrax鈥檚 most dangerous features is its ability to exist as a spore鈥攁n inactive sealed package that can survive extreme conditions outside its host for long periods. Once in the bloodstream, however, the bacterium germinates, triggering a dangerous infection. The activated anthrax bacterium looks like a thin rod swathed in a thick protective capsule coating. This capsule coat lets the bacteria evade macrophages, the roving white blood cells that form the first line of our immune response.
The researchers examined a gene that codes for a particular enzyme called CapD, a protein that helps the bacteria form its protective coating once it enters the body. CapD sits on the surface of the cell, grabs molecules of the capsule鈥檚 building blocks (poly-D-gamma-glutamic acid, or PDGA) and attaches them to the bacteria鈥檚 outer wall to form its shield.
鈥淭he PDGA peptide construction is unusual; for example, it is made with the 鈥楧鈥� isomer of glutamic acid instead of the 鈥楲鈥� form found in proteins,鈥� said Andrzej Joachimiak, a co-author of the study. 鈥淭his is why macrophages can鈥檛 deal with the protective capsule of anthrax. They could easily find a regular peptide made of 鈥楲鈥� amino acids, but this is a unique configuration, and they can鈥檛 recognize it. That鈥檚 how they fool the system.鈥�
Joachimiak and the team wanted to map out the crystal structure of CapD. Once the researchers discovered the enzyme's structure, they could begin to search for a molecule that could block its function鈥攚hich in turn would make the bacteria more vulnerable to human defenses.
By using brilliant X-rays at the Structural Biology Center 19ID beamline at Argonne's Advanced Photon Source, the team was able to image two versions of the protein: one with a molecule of imitation capsule material attached, and one without.
鈥淚t looks like Pac-Man,鈥� Joachimiak said. 鈥淭he jaws are open when it鈥檚 empty, but when the ligand attaches, it clamps down around it.鈥� Then the enzyme cleaves the polymer and attaches it to the surface of the cell.
The paper, 鈥溾��, will be published in the Journal of Biological Chemistry.
The work to characterize anthrax and other pathogenic or important bacteria is part of an initiative by the Midwest Center for Structural Genomics, an NIH-funded consortium of eight institutions, and the Region V Great Lakes Regional Center of Excellence in Biodefense and Emerging Infectious Diseases Consortium.
Provided by Argonne National Laboratory ( : )
