A team of researchers has just developed an X-ray crystallographic structure of a nicotine receptor called the α4β2 nicotinic receptor. The findings may lead to a better understanding of nicotine addiction. The team is hopeful that their research may also lead to the development of better treatments for patients suffering from addiction. The details are in a paper that was just published in the journal Nature.
The α4β2 (alpha-4-beta-2) nicotinic receptor is a protein found in the brain. Nicotine binds to this receptor, leading to the effects caused by smoking cigarettes or using chewing tobacco. While some of these effects are largely benign, the binding of nicotine to the α4β2 nicotinic receptor can also lead to nicotine addiction. Researchers had tried to crystallize this protein in order to better study it, but every previous method had failed.
Researchers from the O’Donnell Brain Institute developed a new technique for isolating and crystallizing the structure of α4β2. They designed a virus that would infect cells and produce tons of the receptor, allowing the team to then extract large amounts of α4β2 protein. The purified sample was induced to crystallize. The team used X-ray diffraction to get a high-resolution version of the receptor’s structure as it was bound to nicotine. The 3-D model will make it easier to study the receptor and how it works. The team is continuing their research in order to study the mechanisms and functions of α4β2 nicotinic receptors. The team plans to study the receptors with and without bonded nicotine molecules.
The researchers’ new findings are providing insight into how nicotine interacts with receptors such as the α4β2 nicotinic receptor. The team believes their findings could lead to better treatments for nicotine addiction by analyzing the structure and functions of nicotine receptors. The receptor also plays roles in certain types of mental illness, epilepsy, and dementia. Further research may aid in the development of medications for a variety of illnesses.
Claudio L. Morales-Perez, Colleen M. Noviello & Ryan E. Hibbs. X-ray structure of the human α4β2 nicotinic receptor. Nature (2016).