New insights into P2X7 receptor regulation: Ca2+-calmodulin and GDP bind to the soluble P2X7 ballast domain.
- Resource Type
- Article
- Authors
- Sander, Simon; Müller, Isabel; Garcia-Alai, Maria M.; Nicke, Annette; Tidow, Henning
- Source
- Journal of Biological Chemistry. Oct2022, Vol. 298 Issue 10, p1-9. 9p.
- Subject
- *CALMODULIN
*SMALL-angle X-ray scattering
*LIGAND binding (Biochemistry)
*GROSS domestic product
- Language
- ISSN
- 0021-9258
P2X7 receptors are nonselective cation channels that are activated by extracellular ATP and play important roles in inflammation. They differ from other P2X family members by a large intracellular C-terminus that mediates diverse signaling processes that are little understood. A recent cryo-EM study revealed that the C-terminus of the P2X7 receptor forms a unique cytoplasmic ballast domain that possesses a GDP-binding site as well as a dinuclear Zn2+ site. However, the molecular basis for the regulatory function of the ballast domain as well as the interplay between the various ligands remain unclear. Here, we successfully expressed a soluble trimeric P2X7 ballast domain (P2X7BD) and characterized its ligand binding properties using a biophysical approach. We identified calmodulin (CaM)-binding regions within the ballast domain and found that binding of Ca2+-CaM and GDP to P2X7BD have opposite effects on its stability. Small-angle X-ray scattering experiments indicate that Ca2+-CaM binding disrupts the trimeric state of P2X7BD. Our results provide a possible framework for the intracellular regulation of the P2X7 receptor. [ABSTRACT FROM AUTHOR]