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SUMMARY:LMB Seminar: Structural basis of how the BIRC6/SMAC complex regula
 tes apoptosis and autophagy - Tim Clausen\, Research Institute of Molecula
 r Pathology (IMP)
DTSTART:20221208T100000Z
DTEND:20221208T110000Z
UID:TALK192437@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic p
 roteases\, keeping them inactive and preventing cell death. The atypical u
 biquitin ligase BIRC6 is the only essential IAP\, additionally functioning
  as a suppressor of autophagy. Little is known of the mechanism how BIRC6 
 fulfills these two roles. Here\, we performed a structure-function analysi
 s of BIRC6 in complex with caspase-9\, HTRA2\, SMAC\, and LC3B which are c
 ritical apoptosis and autophagy proteins. Cryo-EM structures show BIRC6 fo
 rms a megadalton crescent shape that arcs around a spacious cavity contain
 ing receptor sites for client proteins. Multivalent binding of SMAC obstru
 cts client binding\, impeding ubiquitination of both autophagy and apoptot
 ic substrates. These data reveal the molecular mechanism of how the stress
  induced BIRC6/SMAC complex assembles a central hub regulating apoptosis a
 nd autophagy
LOCATION:In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoo
 m\, link: https://mrc-lmb-cam-ac-uk.zoom.us/j/94050407947?pwd=ZFZZYkxhd0Js
 bGJuMFNHQnlzOSsydz09
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