000007583 001__ 7583
000007583 005__ 20240124114246.0
000007583 0247_ $$2DOI$$a10.6083/0p0967470
000007583 037__ $$aETD
000007583 245__ $$aGating and modulation of acid-sensing ion channels
000007583 260__ $$bOregon Health and Science University
000007583 269__ $$a2019
000007583 336__ $$aDissertation
000007583 502__ $$bPh.D.
000007583 520__ $$aBy leveraging the inhibitory effects of divalent cations Ca2+ and Ba2+, I determined the structure of a homotrimeric ASIC in a high pH resting conformation by both x-ray crystallography and cryo-electron microscopy (cryo-EM). These results demonstrated that collapse of the acidic pocket is required for proton-dependent activation and that flexible linkers within the palm domain rearrange to enable channel desensitization. Moreover, the location of state-dependent Ba2+ sites within the acidic pocket and central vestibule, determined by anomalous scattering x-ray crystallography, indicates that inhibition of proton-dependent gating by divalent cations is at least partly due to competition for similar binding sites.
000007583 542__ $$fIn copyright - single owner
000007583 650__ $$aIon Channels$$021013
000007583 650__ $$aSodium Channels$$028231
000007583 650__ $$aMembrane Proteins$$022009
000007583 6531_ $$aacid sensing ion channel
000007583 6531_ $$aasic channel
000007583 691__ $$aSchool of Medicine$$041369
000007583 7001_ $$aYoder, Nathan B.
000007583 8564_ $$9769fe76b-57d9-495a-8974-5939ec72f830$$s38095982$$uhttps://digitalcollections.ohsu.edu/record/7583/files/yoder.nathan.2019.pdf
000007583 905__ $$a/rest/prod/0p/09/67/47/0p0967470
000007583 909CO $$ooai:digitalcollections.ohsu.edu:7583$$pstudent-work
000007583 980__ $$aTheses and Dissertations