Researchers from Weill Cornell Medicine have found that the molecules cAMP and cGMP have subtle differences in their binding to their signaling partners, leading to their distinct effects. Their study, published in Nature Structural & Molecular Biology, used a sensitive measurement technique to reveal at the single-molecule level how cAMP and cGMP bind to an ion channel. This research illuminates the fundamental mechanism of how cAMP and cGMP work as regulators in various biological roles and could eventually lead to new treatments for disorders involving ion channel malfunctions.
Both molecules, referred to as cyclic nucleotides, are part of the same family as the nucleotide building blocks A and G of DNA. While one molecule is often the activator, the other molecule does little but can force a target into an inactive state by binding to the same site, hence the competition between the two molecules switches the channels on and off. The proteins regulated by cAMP/cGMP include a large class of ion channels called cyclic nucleotide-gated (CNG) ion channels, which have crucial roles across the nervous system, including in the sensory neurons mediating smell and vision, and in the pacemaker cells that govern heartbeat rhythm.
“We found clear differences in the interaction and binding strength of these two molecules to the ion channels, which we think explains why one can open the channel and the other cannot,” said Dr. Simon Scheuring, a professor of physiology and biophysics in anesthesiology at Weill Cornell Medicine, and senior author of the study. The team used atomic force microscopy (AFM) and a force-sensing method to measure the binding force of just one cAMP or cGMP molecule to its binding site on the ion channel.
The researchers believe that their findings already advance the understanding of a fundamental aspect of cell biology, and plan future studies with mammalian CNG channels.
More information:
Yangang Pan et al, Discrimination between cyclic nucleotides in a cyclic nucleotide-gated ion channel, Nature Structural & Molecular Biology (2023). DOI: 10.1038/s41594-023-00955-3
Citation:
How the ancient messengers cAMP and cGMP deliver their messages (2023, May 9)
retrieved 9 May 2023
from https://phys.org/news/2023-05-ancient-messengers-cgmp-messages.html
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