Oregon Health & Science University
Designed to detect pH fluctuations, acid-sensing ion channels began as mystifying molecules, initially known to only gate upon proton binding. However, recent studies unveiled a new mode of gating, independent of pH, thus revealing new roles in which they participate in the central and peripheral nervous systems. Harboring a large extracellular domain and anchored to the membrane bilayer with six transmembrane domains, these channels desensitize on a timescale of seconds, thus complicating structural studies investigating mechanisms underlying ion channel gating. To stabilize the activated state of the channel, I utilized potent and highly specific toxins and determined crystal structures of acid-sensing ion channel 1a in complexes with PcTx1 and MitTx, toxins identified from the venom of spider and snake, respectively, locking the channel in distinct open conformations. The structures illustrate that toxins bind at the subunit interface. Whereas the small PcTx1 binds near the acidic p
Neuroscience Graduate Program
School of Medicine
Baconguis, Isabelle Ryssa Joe Eduria, "Structural plasticity and dynamic selectivity of acid-sensing ion channel - toxin complexes" (2012). Scholar Archive. 866.