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 What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>