Deep learning structural insights into heterotrimeric alternatively spliced P2X7 receptors.

P2X7 receptors (P2X7Rs) are membrane-bound ATP-gated ion channels that are composed of three subunits. Different subunit structures may be expressed due to alternative splicing of the P2RX7 gene, altering the receptor's function when combined with the wild-type P2X7A subunits. In this study, the application of the deep-learning method, AlphaFold2-Multimer (AF2M), for the generation of trimeric P2X7Rs was validated by comparing an AF2M-generated rat wild-type P2X7A receptor with a structure determined by cryogenic electron microscopy (cryo-EM) (Protein Data Bank Identification: 6U9V).

Alternatively Spliced Isoforms of the P2X7 Receptor: Structure, Function and Disease Associations.

The P2X7 receptor (P2X7R) is an ATP-gated membrane ion channel that is expressed by multiple cell types. Following activation by extracellular ATP, the P2X7R mediates a broad range of cellular responses including cytokine and chemokine release, cell survival and differentiation, the activation of transcription factors, and apoptosis. The P2X7R is made up of three P2X7 subunits that contain specific domains essential for the receptor's varied functions.