000000863 001__ 863 000000863 005__ 20260120144839.0 000000863 0247_ $$2DOI$$a10.6083/M43F4MNQ 000000863 037__ $$aETD 000000863 245__ $$aStructural plasticity and dynamic selectivity of acid-sensing ion channel - toxin complexes 000000863 260__ $$bOregon Health and Science University 000000863 269__ $$a2012 000000863 336__ $$aThesis 000000863 502__ $$bPh.D. 000000863 502__ $$gNeuroscience 000000863 520__ $$aAcid-sensing ion channels (ASICs), initially thought to gate solely via proton binding, have been shown to activate through pH-independent mechanisms, revealing diverse roles in the nervous system. To stabilize activated states, we determined crystal structures of ASIC1a bound to spider toxin PcTx1 and snake toxin MitTx. PcTx1 binds near the acidic pocket, while MitTx wedges between subunits, inducing distinct conformational changes. Structural comparisons highlight conserved scaffolds and dynamic regions that mediate gating and ion selectivity. These findings elucidate toxin-binding mechanisms and channel activation, providing a foundation for therapeutic targeting of ASICs. 000000863 540__ $$fCC BY 000000863 542__ $$fIn copyright - single owner 000000863 650__ $$aIon Channels$$021013 000000863 650__ $$aMembrane Proteins$$022009 000000863 650__ $$aCrystallography$$017234 000000863 650__ $$aVenoms$$027764 000000863 650__ $$aAcid Sensing Ion Channels$$040087 000000863 650__ $$aIon Channel Gating$$028538 000000863 650__ $$aSnake Venoms$$026086 000000863 650__ $$aCrystallography, X-Ray$$030746 000000863 691__ $$aSchool of Medicine$$041369 000000863 692__ $$aVollum Institute$$041509 000000863 7001_ $$aBaconguis, Isabelle$$uOregon Health and Science University$$041354 000000863 7201_ $$aGouaux, Eric$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor 000000863 8564_ $$9f1a2bfdc-63bc-449a-bad6-cf4f729cbe48$$s4429046$$uhttps://digitalcollections.ohsu.edu/record/863/files/866_etd.pdf$$ePublic$$2ccab5343295eef5421614fa51c628ab4$$31 000000863 905__ $$a/rest/prod/xd/07/gs/75/xd07gs75z 000000863 909CO $$ooai:digitalcollections.ohsu.edu:863$$pstudent-work 000000863 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000000863 980__ $$aTheses and Dissertations