TY  - GEN
N2  - 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.
DO  - 10.6083/0p0967470
DO  - DOI
AB  - 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.
T1  - Gating and modulation of acid-sensing ion channels
DA  - 2019
AU  - Yoder, Nathan B.
L1  - https://digitalcollections.ohsu.edu/record/7583/files/yoder.nathan.2019.pdf
PB  - Oregon Health and Science University
PY  - 2019
ID  - 7583
L4  - https://digitalcollections.ohsu.edu/record/7583/files/yoder.nathan.2019.pdf
KW  - Ion Channels
KW  - Sodium Channels
KW  - Membrane Proteins
KW  - acid sensing ion channel
KW  - asic channel
TI  - Gating and modulation of acid-sensing ion channels
Y1  - 2019
L2  - https://digitalcollections.ohsu.edu/record/7583/files/yoder.nathan.2019.pdf
LK  - https://digitalcollections.ohsu.edu/record/7583/files/yoder.nathan.2019.pdf
UR  - https://digitalcollections.ohsu.edu/record/7583/files/yoder.nathan.2019.pdf
ER  -