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Cryo electron microscopy structure of the ATP-gated rat P2X7 ion channel in the ATP-bound, open state
Structural highlights
FunctionP2RX7_RAT Receptor for ATP that acts as a ligand-gated ion channel. Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells. Publication Abstract from PubMedP2X receptors are trimeric, non-selective cation channels activated by extracellular ATP. The P2X7 receptor subtype is a pharmacological target because of involvement in apoptotic, inflammatory, and tumor progression pathways. It is the most structurally and functionally distinct P2X subtype, containing a unique cytoplasmic domain critical for the receptor to initiate apoptosis and not undergo desensitization. However, lack of structural information about the cytoplasmic domain has hindered understanding of the molecular mechanisms underlying these processes. We report cryoelectron microscopy structures of full-length rat P2X7 receptor in apo and ATP-bound states. These structures reveal how one cytoplasmic element, the C-cys anchor, prevents desensitization by anchoring the pore-lining helix to the membrane with palmitoyl groups. They show a second cytoplasmic element with a unique fold, the cytoplasmic ballast, which unexpectedly contains a zinc ion complex and a guanosine nucleotide binding site. Our structures provide first insights into the architecture and function of a P2X receptor cytoplasmic domain. Full-Length P2X7 Structures Reveal How Palmitoylation Prevents Channel Desensitization.,McCarthy AE, Yoshioka C, Mansoor SE Cell. 2019 Oct 17;179(3):659-670.e13. doi: 10.1016/j.cell.2019.09.017. Epub 2019 , Oct 3. PMID:31587896[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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