Fig. 2: The activation of P2X3 receptors may be associated with the interrelated movements of transmembrane domains and intracellular domains (ICD).

A The homology model of the rP2X3 receptor at the open state, observed in parallel to the membrane, with the membrane position indicated by pink dots. Side and bottom perspectives of the ICD of rP2X3 in the right panel, including the delineation of amino acid residue ranges 9–13, 14–20, 347–357, and 358–363. Each of the three subunits is distinctly colored, with the “cytoplasmic cap” composed of three 1α3β domains. B Zoom-in view of critical residues within the 1α3β ___domain of P2X3 receptors (numbered according to rat P2X3, rP2X3), displayed in sticks for emphasis. C Side and bottom views of the interrelated motions of ICD and transmembrane domains in the mode derived from employing membrANM analysis on the hP2X3 receptor. Motion direction is visually emphasized through the use of blue arrows. D Pooled data comparing rP2X3 current density in response to ATP (10 μM) for WT and mutant receptors. Each open circle in the scatter plot represents an individual measurement. Data are expressed as mean ± S.E.M. n = 5 (rP2X3^Y10A, rP2X3^T12A, rP2X3^V16A, rP2X3^I23A, rP2X3^L343A, rP2X3^Y353A, rP2X3^R356A, rP2X3^K357A and rP2X3^E363A), 6 (rP2X3^V18A, rP2X3^S20A, rP2X3^V361A and rP2X3^E359A), or 10 (rP2X3^WT). ^*P < 0.05 and ^**P < 0.01 vs. WT, one-way ANOVA with Dunnett’s multiple comparisons test, P = 0.003 (rP2X3^Y10A, rP2X3^T12A, rP2X3^V16A, rP2X3^I23A, rP2X3^Y353A, rP2X3^K357A), 0.002 (rP2X3^V18A), 0.9743 (rP2X3^S20A), 0.005 (rP2X3^L343A), 0.9996 (rP2X3^R356A), 0.0058(rP2X3^V361A), 0.0001 (rP2X3^E359A), and 0.0459 (rP2X3^E363A).