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 in Science Express.
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.