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SUMMARY:Insights into ligand recognition and desensitization from the x-ra
 y structure of a nicotinic receptor - Ryan Hibbs\, UT Southwestern
DTSTART:20170330T090000Z
DTEND:20170330T100000Z
UID:TALK71872@talks.cam.ac.uk
CONTACT:Robert Jones
DESCRIPTION:Nicotinic acetylcholine receptors are ligand gated ion channel
 s that mediate fast chemical neurotransmission at the neuromuscular juncti
 on and play diverse signaling roles in the central nervous system. The vas
 t majority of these and other pentameric receptors in the superfamily asse
 mble as obligate heteromers. Here I will present methods we developed for 
 expression and biochemical characterization of heteromeric\nion channels a
 nd present the first X-ray crystal structure of a nicotinic\nreceptor.\nTh
 e alpha4beta2 nicotinic receptor that we characterized structurally is the
  most abundant receptor subtype in the brain\, is the principal target in 
 nicotine addiction and its dysfunction is associated with familial epileps
 y. The structure of the receptor in complex with the agonist nicotine reve
 als principles of ligand selectivity among different classes of subunit in
 terfaces in the heteropentameric assembly. The receptor is stabilized by n
 icotine in what we suggest is a non-conducting\, desensitized conformation
 . The constriction point in the permeation pathway is formed at the select
 ivity filter\, located at the cytosolic end of the pore. The desensitized 
 state of this channel provides a distinct structural reference point in th
 e allosteric gating cycle of the larger Cys-loop receptor superfamily.
LOCATION:MRC LMB: Max Perutz Lecture Theatre
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