Fig. 5: PANX1 germline mutant, PANX1R217H alters channel properties.
From: Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms
a A cross-section of superposed structures of PANX1WT (blue) and PANX1R217H (red); the inset shows the altered conformation of the residue (W74) at the extracellular entrance of the pore. The dashed line represents the reduced pore cross-section distance in PANX1R217H(red); the W74 rotates by 80° at the χ2 torsion angle, reducing the pore diameter by 3.8 Å compared to PANX1WT (Supplementary Movie 1). The density corresponding to W74, depicted at 5.0 σ, is illustrated in the PANX1R217H mutant channel. b The residue R75 in PANX1R217H forms a salt bridge interaction with D81 of the adjacent subunit, mirroring the interaction observed in PANX1WT. c The structural superposition of PANX1WT and PANX1R217H exhibits a disrupted hydrogen-bond network, owing to the mutation, displayed in the inset. For clarity, only one subunit is shown, and arrows indicate the direction of the movement of the mutant in comparison to PANX1WT. The distances displayed in the figure are in angstroms (Å). d Weak apparent binding affinity of the PANX1R217H with ATP-γs was determined to be 186 ± 70 µM compared to 18 ± 4 µM of PANX1WT, n = 3 independent experiments, error bar represents S.D.
