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SUMMARY:Understanding the structural basis of TIR-domain assembly formatio
 n in TRAM- and TRIF- dependent TLR signalling
DTSTART:20211125T070000Z
DTEND:20211125T070100Z
DTSTAMP:20261017T024400Z
UID:indico-contribution-4215@events.synchrotron.org.au
DESCRIPTION:Speakers: Jeff Nanson\, Bostjan Kobe\, Mengqi Pan\n\nToll-like
  receptors (TLRs) detect pathogens and endogenous danger\, initiating immu
 ne responses that lead to the production of pro-inflammatory cytokines.  A
 t the same time\, TLR-mediated inflammation is associated with a number of
  pathological states\, including infectious\, autoimmune\, inflammatory\, 
 cardiovascular and cancer-related disorders. This dual role of the pathway
 s has attracted widespread interest from pharmaceutical industries. Cytopl
 asmic signalling by TLRs starts by their TIR (Toll/interleukin-1 receptor)
  domain interacting with TIR domain-containing adaptor proteins MyD88\, MA
 L\, TRIF and TRAM. Combinatorial recruitment of these adaptors via TIR:TIR
  domain interactions orchestrates downstream signalling pathways\, leading
  to induction of the pro-inflammatory genes. Although many constituents of
  the TLR pathways have been identified\, the available information on thei
 r coordinated interactions is limited. Such information is crucial for a m
 echanistic understanding of TLR signalling\, development of therapeutic st
 rategies\, and understanding of the molecular basis of the consequences fo
 r human disease of adaptor polymorphic variants. We have discovered that T
 IR domains can form large assemblies. We hypothesized that TIR domain sign
 alling occurs through a mechanism involving higher-order assembly formatio
 n. In this study we aim to determine the molecular architecture of higher-
 order assemblies formed by TIR domains with a focus on TRAM-TRIF assemblie
 s in the TLR4 and TLR3 pathway.\n\nhttps://events.synchrotron.org.au/event
 /146/contributions/4215/
LOCATION:Online
RELATED-TO:indico-event-146@events.synchrotron.org.au
URL:https://events.synchrotron.org.au/event/146/contributions/4215/
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