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Identification of the protein interactome of the A2A-adenosine receptor

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Discovering the G-protein's vast receptor network

The A2A receptor is a G-protein–coupled receptor with unique structural and functional characteristics. It is also a common drug target given that it is the action site of caffeine.


Of increasing interest in the emerging field of proteomics, researchers are studying the A2A receptor to understand more about the potential usefulness of its trafficking and signalling pathways. The receptor engages several proteins as it makes its way from the site where it is synthesised to its action area (the cell surface) and finally to its disposal site. Experts have reason to believe that the receptor has a very large interactome, which is the network encompassing the entire set of protein-protein interactions. As such, the A2A-receptor is considered an appropriate binding site for several accessory proteins. However, with only a very few of these having been documented, the challenge is to now determine the extensive range of interactions taking place. The 'Identification of the protein interactome of the A2A-adenosine receptor' (Adenosine-receptor) project is investigating which partners the A2A receptor interacts with by characterising its interactome. Working to express the receptor in cells for study of optimal binding conditions and an initial survey of interaction partners, project partners developed several constructs and created stable cell lines. This helped maintain a maximum number of protein interactions for examination, which resulted in identification of a long list of interactors. Using the information from the first set of tests, Adenosine-receptor team members examined the receptor's trafficking and signalling activity to determine how its interactome changes under different conditions. Initial data suggest that compounds inhibiting some of the interactors can affect normal trafficking. Progress has also been made in isolating complexes where the A2A receptor is found. This was done using a mouse brain and will be useful for in vivo study of the interactome. This pioneering work has the potential to enrich our knowledge about the large set of G-coupled protein receptors and their function in organisms. Project achievements are setting the stage for testing A2A-receptor interaction partners, and knowledge gained here may boost drug discoveries for fighting protein-folding diseases.

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