Scientists observed for the first time the molecular structure of the P2X 7 receptor, a protein that plays a key role in cell death, inflammation, and cancer progression. This breakthrough could lead to new ways of treating multiple sclerosis (MS), coronary artery disease, cancer, and inflammation.
The findings were reported in the study, “Full-Length P2X7 Structures Reveal How Palmitoylation Prevents Channel Desensitization,” published in the journal Cell.
P2X receptors are proteins found on the membranes of cells that work as channels, transporting molecules with a positive electrical charge (cations), such as calcium and sodium, in and out of cells. A portion of each of these receptors can be found outside of cells (extracellular domain), while the rest are inside (cytoplasmic domain).
The P2X 7 receptor, a member of the P2X family, has been studied as a therapeutic target because of its association with certain disease processes, such as inflammation, cancer’s spread, and neurodegeneration.
Although researchers anticipated the structure and function of the P2X 7 receptor would be very different from that of other P2X receptors, due to its unique ability to stay open indefinitely after being activated, they did not know which aspects distinguished its molecular structure from other receptors in this family.
Investigators at Oregon Health & Science University (OSHU) used a technique called cryogenic electron microscopy (cryo-EM) to see for the first time the 3D molecular structure of the cytoplasmic domain of the P2X 7 receptor in action.
In this way, they found the cytoplasmic domain of P2X 7 was bound to several groups of fatty acid molecules, a chemical modification known as palmitoylation (the addition of palmitoyl groups).
They watched as the indefinitely open channel allowed cations to freely enter cells, triggering a series of disease processes that led to cell death.
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