Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Botulism bug says no to nitric oxide, provides key to molecule’s role in human cell signaling

08.10.2004


A deadly bacterium’s defense against a mortal molecular enemy illuminates the origins and structure of a vital protein involved in human cell signaling, University of Texas Medical School scientists report today in Science Express, the rapid online publication forum for the journal Science.



The paper also details how evolution transformed one of nature’s simplest molecules, nitric oxide (NO), from a toxin to anaerobic bacteria – the planet’s oldest life form – into a beneficial signaling molecule in higher animals. It also offers an explanation for how the decades-old practice of treating meat with sodium nitrite prevents life-threatening food poisoning known as botulism.

Discovering how botulism-causing Clostridium botulinum detects nitric oxide (NO) sheds light on how NO connects with its receptor protein in humans to govern crucial processes in the cardiovascular, neurological and immunological systems, said senior author C. S. Raman, Ph.D., assistant professor and director of the Structural Biology Research Center in the UT Medical School Department of Biochemistry and Molecular Biology.


"We started by identifying the protein that the botulism bug uses to detect and evade NO," Raman said. "What we have ultimately shown is how this protein evolved from being part of a protective mechanism into a system that learned to use the toxin to benefit the organism."

In human beings, nitric oxide binds to a receptor called soluble guanylyl cyclase to make cyclic GMP, a molecule that improves blood flow by relaxing blood vessel walls. Ferid Murad, M.D., Ph.D., professor and chairman of Integrative Biology and Pharmacology at the UT Medical School at Houston, won the Nobel prize for his 1977 finding that NO is the ingredient that makes nitroglycerine beneficial to heart patients. Since then NO has been found to govern many other vital biological functions and became the basis for medications that treat erectile dysfunction. However, the structural details of soluble guanylyl cyclase have remained elusive, Murad and Raman said. The protein is difficult to crystallize for structural analysis.

During a series of experiments that tracked the evolutionary development of the sensor protein identified in C. botulinum, dubbed SONO for "sensor of NO," the scientists were able to determine the three-dimensional structure of a related nitric oxide sensor in a different bacterium. That structure will provide a key to unlock answers to some questions regarding the human NO receptor, soluble guanylyl cyclase (sGC), Raman said. "Having these structures now will help us attack that problem, because we know that this bacterial version of SONO is very similar to soluble guanylyl cyclase. "If you know the structure of a protein, then you can develop therapeutics targeted to detect specific binding pockets on the molecule," Raman said. "That may allow us to control sGC activity in the absence of nitric oxide in such a way that we can combat cardiovascular and cerebrovascular disease."

And don’t forget meat protection. The research team showed that C. botulinum uses SONO to detect nitric oxide, and then to flee its presence. "It’s a strange topic for a strict vegetarian who has never touched meat in his life," Raman said.

Co-authors of the paper are: First author Pierre Nioche, Ph.D., research fellow in the Structural Biology Research Center; Vladimir Berka, Ph.D., senior research associate and Ah-Lim Tsai, Ph.D., professor, both of the Medical School Division of Hematology; and from the United Kingdom, Julia Vipond of the Health Protection Agency, Porton Down, Salisbury; and Nigel Minton of the Center of Biomolecular Sciences and Institute of Infection, Immunity and Inflammation, University of Nottingham.

Scott Merville | EurekAlert!
Further information:
http://www.uthouston.edu
http://www.uth.tmc.edu

More articles from Life Sciences:

nachricht Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>