Allosteric modulation and G-protein selectivity of the Ca(2+)-sensing receptor. (https://pubmed.ncbi.nlm.nih.gov/38326620/)

These scientists wanted to understand how a special protein called the calcium-sensing receptor (CaSR) works in our bodies. This protein is important for keeping the amount of calcium in our bodies balanced.

To do this, the scientists used a special microscope called cryo-electron microscopy to look at the CaSR protein. They also did some experiments to see how the CaSR protein interacts with other proteins inside our cells.

They found that when the CaSR protein is activated, it changes its shape and interacts with two different proteins called G(i) and G(q). These two proteins help the CaSR protein do its job. The scientists also discovered that certain molecules called polyamines can make the CaSR protein work even better by attaching to different parts of it.

They also found that a specific amino acid called L-tryptophan, which is found in some foods, can attach to the CaSR protein in the same way as a medicine called cinacalcet. This helps us understand how cinacalcet and other medicines can affect the CaSR protein.

Overall, these findings help us understand how the CaSR protein works and how it can be influenced by different molecules. This knowledge can help scientists develop new medicines to treat conditions related to calcium imbalance in our bodies.

He F., Wu CG., Gao Y., Rahman SN., Zaoralova M., Papasergi-Scott MM., Gu TJ., Robertson MJ., Seven AB., Li L., Mathiesen JM., Skiniotis G. Allosteric modulation and G-protein selectivity of the Ca(2+)-sensing receptor. Nature. 2024 Feb 7. doi: 10.1038/s41586-024-07055-2.