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SUMMARY:Gating Mechanisms and drug modulation in Pentameric Ligand-gated I
 on Channels: Insights from Cryo-EM - Prof. Sudha Chakrapani\, Case Western
  Reserve University
DTSTART:20210505T150000Z
DTEND:20210505T160000Z
UID:TALK160030@talks.cam.ac.uk
CONTACT:Akhila Kadgathur Jayaram
DESCRIPTION:My research over the last 20 years has focused on ion channels
  that mediate fast synaptic transmission at the neuronal and neuromuscular
  junctions. Among these channel classes\, the pentameric ligand-gated ion 
 channel (pLGIC) superfamily governs crucial physiological processes such a
 s gastrointestinal functions\, motor functions\, and pain transmission. Ab
 errant channel functions are implicated in neurological disorders\, mood d
 isorders\, addiction\, and chronic pain. Currently used therapeutic strate
 gies suffer from our limited knowledge of the molecular details of pLGIC f
 unction\, the origin of their functional diversity\, and the downstream si
 gnaling events. Using single-particle cryo-electron microscopy\, we solved
  structures of the full-length serotonin receptor (5HT3AR)\, a cationic pL
 GIC\, in the resting state and two serotonin-activated conformations. More
  recently\, we have solved the structures of full-length glycine receptor 
 (GlyR)\, in a membrane environment\, in the resting\, open\, and desensiti
 zed states. Building on these advancements\, we have now determined high-r
 esolution snap-shots of drug-bound conformations of both 5HT3AR and GlyRs.
  Taken together\, these findings provide molecular blueprints of the chann
 el in physiologically relevant conformations for therapeutic targeting and
  pave the way for design of novel therapeutic agents that are safer and mo
 re effective.
LOCATION: https://zoom.us/j/94961379063
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