Washington: Researchers at The University of Texas at Austin and the Pasteur Institute in France have been able to identify how alcohol might affect key brain proteins for the first time - thanks to a rare bacteria that grows only on rocks in the Swiss Alps.
It’s a major step on the road to eventually developing drugs that could disrupt the interaction between alcohol and the brain.
“Now that we’ve identified this key brain protein and understand its structure, it’s possible to imagine developing a drug that could block the binding site,” Adron Harris, professor of biology and director of the Waggoner Center for Alcohol and Addiction at The University of Texas at Austin, said.
Harris and his former postdoctoral fellow Rebecca Howard, now an assistant professor at Skidmore College, are co-authors on the paper.
It describes the structure of the brain protein, called a ligand-gated ion channel, that is a key enabler of many of the primary physiological and behavioral effects of alcohol.
Harris said that for some time there has been suggestive evidence that these ion channels are important binding sites for alcohol.
Researchers couldn’t prove it, however, because they couldn’t crystallize the brain protein well enough, and therefore couldn’t use X-ray crystallography to determine the structure of the protein with and without alcohol present.
“For many of us in the alcohol field, this has been a Holy Grail, actually finding a binding site for alcohol on the brain proteins and showing it with X-ray crystallography,” Harris said. “But it hasn’t been possible because it is not possible to get a nice crystal.”
The breakthrough came when Marc Delarue and his colleagues at the Pasteur Institute sequenced the genome of cyanobacteria Gloeobacter violaceus.
They noted a protein sequence on the bacteria that is remarkably similar to the sequence of a group of ligand-gated ion channels in the human brain. They were able to crystallize this protein. Harris saw the results and immediately got in touch.
“This is something you never would have found with any sort of logical approach,” he said.
“You never would have guessed that this obscure bacterium would have something that looks like a brain protein in it. But the institute, because of Pasteur’s fascination with bacteria, has this huge collection of obscure bacteria, and over the last few years they’ve been sequencing the genomes, keeping an eye out for interesting properties,” he added.
The study is published in the journal Nature Communications.