Gating and modulation of acid-sensing ion channels Public Deposited

By leveraging the inhibitory effects of divalent cations Ca2+ and Ba2+, I determined the structure of a homotrimeric ASIC in a high pH resting conformation by both x-ray crystallography and cryo-electron microscopy (cryo-EM). These results demonstrated that collapse of the acidic pocket is required for proton-dependent activation and that flexible linkers within the palm domain rearrange to enable channel desensitization. Moreover, the location of state-dependent Ba2+ sites within the acidic pocket and central vestibule, determined by anomalous scattering x-ray crystallography, indicates that inhibition of proton-dependent gating by divalent cations is at least partly due to competition for similar binding sites.

  • yoder.nathan.2019.pdf
Publication Date
  • 2019
Document type