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


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:

More articles from Life Sciences:

nachricht When fat cells change their colour
28.10.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Prototype device for measuring graphene-based electromagnetic radiation created

28.10.2016 | Power and Electrical Engineering

Gamma ray camera offers new view on ultra-high energy electrons in plasma

28.10.2016 | Physics and Astronomy

When fat cells change their colour

28.10.2016 | Life Sciences

More VideoLinks >>>