P2X Purinoreceptor - Basic Structure and Nomenclature

Basic Structure and Nomenclature

To date, seven separate genes coding for P2X subunits have been identified, and named to as P2X₁ through P2X₇.

The subunits all share a common topology, possessing two plasma membrane spanning domains, a large extracellular loop and intracellular carboxyl and amino termini (Figure 1) The amino termini contain a consensus site for protein kinase C phosphorylation, indicating that the phosphorylation state of P2X subunits may be involved in receptor functioning. Additionally, there is a great deal of variability in the C termini, indicating that they might serve subunit specific properties.

Generally speaking, most subunits can form functional homomeric or heteromeric receptors. Receptor nomenclature dictates that naming is determined by the constituent subunits; e.g. a homomeric P2X receptor made up of only P2X₁ subunits is called a P2X₁ receptor, and a heteromeric receptor containing P2X₂ and P2X₃ subunits is called a P2X_2/3 receptor. The general consensus is that P2X₆ cannot form a functional homomeric receptor and that P2X₇ cannot form a functional heteromeric receptor.

Evidence from early molecular biological and functional studies has strongly indicated that the functional P2X receptor protein is a trimer, with the three peptide subunits arranged around an ion-permeable channel pore. This view was recently confirmed by the use of X-ray crystallography to resolve the three-dimensional structure of the zebrafish P2X₄ receptor(Figure 2). These findings indicate that the second transmembrane domain of each subunit lines the ion-conducting pore and is therefore responsible for channel gating.

The relationship between the structure and function of P2X receptors has been the subject of considerable research, and key protein domains responsible for regulating ATP binding, ion permeation, pore dilation and desensitization have been identified.