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Aargau researchers uncover the secrets of cells

Researchers at the Paul Scherrer Institute have successfully depicted the structure of a protein that plays a key role in transmitting information into a cell. The results could help to develop new drugs for diseases such as type 2 diabetes.

PSI
PSI biochemist Volodymyr Korkhov (right) and Chao Qi, first author of the study, preparing a sample for cryo-electron microscopy. Image Credit: Paul Scherrer Institute/Mahir Dzambegovic

The interior of all living cells is protected by a membrane. These membranes also contain mechanisms which allow specific substances or information inside the cell. According to information from the Paul Scherrer Institute (PSI), this signal pathway comprises three components: The first is a receptor that recognizes the signal and is activated by it. The second is known as a “G protein” – this binds to the activated receptor and transmits the signal to one or more effector proteins. The effector protein or effector proteins are the third component. They produce a secondary messenger called cyclic AMP (cAMP), which in turn triggers a reaction in the cell.

PSI researchers have now been able to depict the effector protein – in this case adenylyl cyclase – and have produced the most detailed image to date of this type of membrane protein. Volodymyr Korkhov, head of the research group, commented: “To understand how signal pathways in the cell work, it is necessary first to know what the components involved look like in detail”.

This new insight into the molecular structure of adenylyl cyclase provides a much better understanding of how external signals lead to the controlled production of the important secondary messenger cAMP. The concentration of cAMP in cells plays an important role in the development of cardiovascular diseases, certain tumors, and type 2 diabetes.

“In the future, our new findings could make it possible to identify drugs that inhibit or activate the adenylyl cyclase, depending on whether overproduction or lack of cAMP is responsible for a disease”, Korkhov explains.

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