BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//talks.cam.ac.uk//v3//EN
BEGIN:VTIMEZONE
TZID:Europe/London
BEGIN:DAYLIGHT
TZOFFSETFROM:+0000
TZOFFSETTO:+0100
TZNAME:BST
DTSTART:19700329T010000
RRULE:FREQ=YEARLY;BYMONTH=3;BYDAY=-1SU
END:DAYLIGHT
BEGIN:STANDARD
TZOFFSETFROM:+0100
TZOFFSETTO:+0000
TZNAME:GMT
DTSTART:19701025T020000
RRULE:FREQ=YEARLY;BYMONTH=10;BYDAY=-1SU
END:STANDARD
END:VTIMEZONE
BEGIN:VEVENT
CATEGORIES:Neurobiology
SUMMARY:K2P channel structure\, function\, and chemical bi
 ology: Driving a wedge into a cryptic modulatory s
 ite  - Dan Minor\, Professor
DTSTART;TZID=Europe/London:20170904T140000
DTEND;TZID=Europe/London:20170904T150000
UID:TALK79111AThttp://talks.cam.ac.uk
URL:http://talks.cam.ac.uk/talk/index/79111
DESCRIPTION:Polymodal thermo- and mechanosensitive two-pore do
 main potassium (K2P) channels of the TREK subfamil
 y generate 'leak' currents that regulate neuronal 
 excitability\, respond to lipids\, temperature and
  mechanical stretch\, and influence pain\, tempera
 ture perception and anaesthetic responses.  In con
 trast to other potassium channels\, K2P channels u
 se a selectivity filter 'C-type' gate as the princ
 ipal gating site.  K2P channels stuffer from a poo
 r pharmacological profiles that has limited mechan
 istic and biological studies. We recently discover
 ed a class of small-molecule TREK activators that 
 directly stimulate the C-type gate by acting as mo
 lecular wedges. Structural studies of K2P2.1 (TREK
 -1) alone and with two selective activators unmask
  a cryptic binding pocket unlike other ion channel
  small-molecule binding sites. Our work defines a 
 druggable K2P site that stabilizes the C-type gate
  'leak mode' and provides direct evidence for K2P 
 selectivity filter gating. Our studies define a ne
 w means for ion channel control and offer a new di
 rection for developing a chemical biology for K2P 
 channels.
LOCATION:Lecture Theatre\, MRC Laboratory of Molecular Biol
 ogy (LMB)
CONTACT:Paula Murphy
END:VEVENT
END:VCALENDAR