With their discovery of a new model on the behavior of the nicotinic acetylcholine receptor or nAChR, researchers from the University of Pennsylvania have shed new light on the role of cholesterol and its interaction with protein in muscle and brain tissues.
These researchers demonstrated with the use of existing data on cholesterol and several computers processors that in addition to external sites, nAChR also has several internal sites that can hold cholesterol, which in turns stabilize the structure of the said protein. Through molecular stimulations, the Penn researchers were also able to show that both external and internal sites require cholesterol to support the interaction of the receptor’s agonist-binding domain and its pores, which are said to be essential to its activation.
“The result was surprising because, according to most traditional biological models, cholesterol is part of the membrane, not part of the protein. Our model takes cholesterol out of a background role in the protein’s structure and function and puts it on center stage,” Grace Brannigan, a researcher with the Center for Molecular Modeling at Penn, explained.
Nicotinic acetylcholine receptor is a well-studied protein that is involved in a number of diseases and health conditions such as Alzheimer’s disease, schizophrenia, Parkinson’s disease, epilepsy, inflammation, anesthetics effects, and alcohol, nicotine, and cocaine addiction.
The new model brings with it a lot of implications to the field of pharmacology, among others. Drug development have traditionally taken into account the chemical make-up and structure of the said receptor and with the new Penn research debunking previous models, reexamination of old ways and several years of researchers is underway.
Overall, the new Penn research and model brings with it a major shift in the understanding of nAChR in a lot of aspects: shape, structure, interaction with the environment, and response to neurotransmitters.
On a more general note, the newfound role of the function of cholesterol in relation to protein also have implications on the understanding of recent data which shows that low level of cholesterol in brain cells have harmful effects on a person’s memory, mood and concentration.
Furthermore, a lot of previous theories and studies on the role of cholesterol in brain cells focused mainly on the effect of the said substance on the cell membranes. This breakthrough study of the Penn researchers indicate that cholesterol may have a more direct role if it is indeed buried within the proteins which foster communication between cells.
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