Cells communicate with each other via ‘receptor proteins’ on the cell membranes which are targets for drugs to alter functioning and physiology. However, the latest study from Amitabha Chattopadhyay’s lab at CSIR-Centre for Cellular and Molecular Biology (CCMB) makes a case for designing new drugs to focus on the lipid environment surrounding these receptor proteins.
The lab had earlier found that the serotonin receptors are sensitive to cholesterol surrounding them.
In the new study published in ‘Science Advances’, they report a sensor region on ‘human serotonin1A’ receptor can detect cholesterol, specifically a region called ‘CRAC motifs’, which are believed to interact with cholesterol, said an official release on Tuesday.
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Researchers replaced the specific amino acids in these CRAC motifs and came across a particular amino acid responsible for cholesterol-sensitive function. They collaborated with Jana Selent’s group from Pompeu Fabra University Hospital del Mar Medical Research Institute in Barcelona, Spain, to visualise the protein-cholesterol interaction via computer-aided molecular dynamics simulations.
This helped them predict how the specific amino acid on CRAC motif enables the receptor proteins to sense changes in cholesterol levels by controlling molecular motion in certain regions.
“Cholesterol levels change in our cells with age and in disease conditions. We believe our work will help in developing better drugs that keep in mind not just the receptor proteins as the drug target, but also the lipid environment in which it is present,” said Mr Chattopadhyay.
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“Our expertise in structural biology at CCMB is key towards physical understanding of cells and their functions. This not only adds to the detailed view of living cells but also have immense potential in therapeutics development”, said CCMB director Vinay Nandicoori.