Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UW researchers find second anthrax toxin receptor

08.04.2003


Building on their 2001 discovery of a cellular doorway used by anthrax toxin to enter cells, University of Wisconsin Medical School researchers have found a second anthrax toxin doorway, or receptor. The finding could offer new clues to preventing the toxin’s entrance into cells.

The researchers also have found that when they isolated a specific segment of the receptor in the laboratory, they could use it as a decoy to lure anthrax toxin away from the real cell receptors, preventing much of the toxin from entering cells and inflicting its usually fatal damage.

The findings will appear in this week’s (the week of April 7) online "Early Edition" of the Proceedings of the National Academy of Sciences (http://www.pnas.org).



The new details on the way anthrax toxin enters cells should provide pharmaceutical companies with important new ammunition to attack the grave problem of anthrax disease, says lead researcher John A. T. Young, the Howard M. Temin Professor of Cancer Research at the Medical School’s McArdle Laboratory for Cancer Research.

"This discovery gives scientists more tools to understand how the anthrax toxin works," says Young, adding that he and his team were very surprised to find the second receptor, since the prevailing theory had been that only one exists. Heather Scobie, G. Jonah Rainey and Kenneth Bradley were team members and co-authors on the paper.

The existence of two receptors makes it clear that the toxin’s entry into cells is much more complicated than previously thought, notes Young, an expert on receptor molecules.

Scientists do know that to prevent anthrax disease, antibiotics must be administered immediately to kill anthrax bacteria that typically enter the body as spores via the skin, lungs or gastrointestinal tract. Once activated, the spores become bacteria and soon release toxins consisting of three components.

One toxic component, protective antigen (PA), must attach, or bind, to a receptor before the rest of the toxin can enter cells. Once attached, PA transports the other components - edema factor and lethal factor - into the cells, where they produce effects that can lead quickly to devastating disease symptoms.

Following their 2001 discovery of anthrax toxin receptor (ATR), the UW researchers worked with a protein that has similar molecular features. They chose the protein - called human capillary morphogenesis protein 2, or CMG2 - because it contains an important segment that is somewhat similar to that found in ATR. The segment is the part of the molecule that attaches directly to PA.

"We thought we would use CMG2 as a starting point to make genetic changes to find which characteristics of ATR are important to receptor binding," says Young. "To our surprise, we found that CMG2 itself is an anthrax toxin receptor."

The occurrence of multiple receptors - on the same or different cells - is not uncommon, says Young, citing HIV as an example of a pathogen that employs two major co-receptors to enter cells.

The existence of the two anthrax toxin receptors should interest cancer researchers, as both receptors are turned on when new blood vessels are forming - a process called angiogenesis, Scobie says.

"This may explain anthrax toxin’s effectiveness in treating cancer, which has been shown in studies by other scientists," she adds. "The toxin may have prevented the development of tumor-promoting angiogenesis."

In their previous work, Young and his colleagues used a laboratory-made version of the specific ATR segment that attaches to anthrax toxin as a decoy, and found it to be successful in preventing the toxin from entering the cell. Performing the same exercise with CMG2, they found the new decoy even more effective at enticing the toxin away from the real receptor.

"The new decoy is remarkably potent," says Rainey. "With a ratio of three parts CMG2 decoy to one part toxin, we found that we could effectively neutralize the toxin. Much more of the ATR decoy was required to be effective."

Young said his team now is trying to understand why the new decoy works better.

"We are trying to further improve its function. Our hope is that an improved form of the decoy could be used therapeutically," he says.

The research is supported by a grant from the National Institute of Allergy and Infectious Diseases.


- Dian Land, (608) 263-9893, dj.land@hosp.wisc.edu


John Young | University of Wisconsin-Madison
Further information:
http://www.news.wisc.edu/releases/view.html?id=8477&month=Apr&year=2003

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>