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SUMMARY:Understanding the structural basis of TIR-domain assembly formatio
 n in TRAM- and TRIF- dependent TLR signalling
DTSTART;VALUE=DATE-TIME:20211125T070000Z
DTEND;VALUE=DATE-TIME:20211125T070100Z
DTSTAMP;VALUE=DATE-TIME:20260306T082402Z
UID:indico-contribution-4215@events01.synchrotron.org.au
DESCRIPTION:Speakers: Mengqi Pan ()\nToll-like receptors (TLRs) detect pat
 hogens and endogenous danger\, initiating immune responses that lead to th
 e production of pro-inflammatory cytokines.  At the same time\, TLR-mediat
 ed inflammation is associated with a number of pathological states\, inclu
 ding infectious\, autoimmune\, inflammatory\, cardiovascular and cancer-re
 lated disorders. This dual role of the pathways has attracted widespread i
 nterest from pharmaceutical industries. Cytoplasmic signalling by TLRs sta
 rts by their TIR (Toll/interleukin-1 receptor) domain interacting with TIR
  domain-containing adaptor proteins MyD88\, MAL\, TRIF and TRAM. Combinato
 rial recruitment of these adaptors via TIR:TIR domain interactions orchest
 rates downstream signalling pathways\, leading to induction of the pro-inf
 lammatory genes. Although many constituents of the TLR pathways have been 
 identified\, the available information on their coordinated interactions i
 s limited. Such information is crucial for a mechanistic understanding of 
 TLR signalling\, development of therapeutic strategies\, and understanding
  of the molecular basis of the consequences for human disease of adaptor p
 olymorphic variants. We have discovered that TIR domains can form large as
 semblies. We hypothesized that TIR domain signalling occurs through a mech
 anism involving higher-order assembly formation. In this study we aim to d
 etermine the molecular architecture of higher-order assemblies formed by T
 IR domains with a focus on TRAM-TRIF assemblies in the TLR4 and TLR3 pathw
 ay.\n\nhttps://events01.synchrotron.org.au/event/146/contributions/4215/
LOCATION:Online
URL:https://events01.synchrotron.org.au/event/146/contributions/4215/
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