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SUMMARY:The importance of thermostability and its application to the struc
 ture determination of GPCRs - Dr Chris Tate\, LMB
DTSTART:20121024T091500Z
DTEND:20121024T101500Z
UID:TALK40327@talks.cam.ac.uk
CONTACT:23791
DESCRIPTION:Structural studies of G protein-coupled receptors (GPCRs) are 
 hampered by their lack of stability in detergents and their conformational
  flexibility. We have developed a mutagenic strategy combined with a radio
 ligand binding assay to isolate thermostable mutants of GPCRs biased towar
 ds specific conformations. This has allowed us to determine the structures
  of the b1-adrenergic receptor\, adenosine A2A receptor and neurotensin re
 ceptor bound to either agonists\, partial agonists\, inverse agonists or b
 iased agonists. In addition\, structures of the adenosine A2A receptor wer
 e determined that were used to develop preclinical candidates for the trea
 tment of Parkinson’s disease. I will discuss the strategies used for the
 rmostabilisation\, expression and crystallisation\, and highlight a few of
  the biological insights into mechanism revealed by the GPCR structures. 
LOCATION:Perham's seminar room
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