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 'Lipid asymmetry' plays key role in activating immune cells
20.02.2018 | Biophysical Society

nachricht New printing technique uses cells and molecules to recreate biological structures
20.02.2018 | Queen Mary University of London

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

'Lipid asymmetry' plays key role in activating immune cells

20.02.2018 | Life Sciences

MRI technique differentiates benign breast lesions from malignancies

20.02.2018 | Medical Engineering

Major discovery in controlling quantum states of single atoms

20.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>