Neurons' signaling can be altered by mirror-image molecules. With the help of some sea slugs, chemists from the University of Nebraska-Lincoln have found that one of the smallest possible changes to a biomolecule can elicit one of the grandest conceivable consequences: directing the activation of n
Nebraska chemists have found that a natural, ultra-minor alteration to a molecule can dictate which neuron receptors a neurotransmitter will activate. Though the team discovered the phenomenon in a species of sea slug being held by chemist James Checco, the findings should apply to a range of animals — potentially even humans.
A basic rendering of the left and right hands of the same amino acid. Credit: University of Nebraska-Lincoln Checco’s interest in neuropeptide signaling dates back to his time as a postdoctoral researcher, when he came across the first study to show evidence of a peptide with a D-amino acid activating a neuron receptor in sea slugs. That particular receptor responded to the peptide only when it contained the D-amino acid, making its flip from L to D akin to an on/off switch.
“We were left wondering: Is this the whole story?” Checco said. “What’s really going on? Why make this D molecule if it’s even worse at activating the receptor?”, hint at an answer inspired by a hypothesis. Maybe, the team thought, there were other receptors in the sea slug sensitive to that D-containing peptide. If so, maybe some of those receptors would respond differently to it.
In effect, the team realized, the orientation of that lone amino acid was directing its peptide to activate either one receptor or the other. In its all-L state, the neurotransmitter preferred Checco’s original. When that certain L turned D, on the other hand, it went for Yussif’s new candidate instead.
“I think it is likely that we will find peptides with this kind of modification in humans,” Checco said. “And that’s going to potentially open up new therapeutic avenues in terms of that specific target. Understanding more about how these things are functioning could be exciting there.”
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