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Signalling by Cooperative Assembly Formation (SCAF) by TIR Domains in Innate Immunity and Cell Death Pathways

Published on Feb 4, 202563 Views

TIR (Toll/interleukin-1 receptor) domains are widely distributed in animals, plants and bacteria. They function through self-association and interactions with other TIR domains [1]. They feature in pr

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Presentation

Signalling by cooperative assembly formation (SCAF) by TIR domains in innate immunity and cell death pathways00:00
Innate immunity pathways02:48
TIR domains05:24
Two surprising features of TIR-domain function06:38
Crystal structure of RPS4TIR/RRS1TIR complex07:46
Toll-like receptor signaling09:08
Reversible MALTIR precipitation10:12
Cryo-EM structure of MALTIR filament12:02
MALTIR promotes assembly of MyD88TIR13:35
MicroED of MyD88TIR microcrystals14:38
Serial femtosecond crystallography of MyD88TIR microcrystals15:38
MyD88TIR and MALTIR assemblies16:35
Other MyD88TIR assemblies?17:23
TRIFTIR and TRAMTIR form analogous assemblies18:04
MALTIR and TLR4TIR co-assemble into filaments19:02
Helical reconstruction cryo-EM structure of TLR4TIR-MALTIR co-filament19:55
Signalling requires TLR4TIR head-to-tail interactions22:34
SCAF (signaling by cooperative assembly formation) by TIR domains in the TLR4 pathway23:50
Signaling by cooperative assembly formation (SCAF)25:04
Programmed (Wallerian) axon degeneration28:01
Axon degeneration pathway28:44
SARM1 structure30:12
NMR assay for NADase activity by SARM1TIR30:53
NADase activity by SARM1TIR31:51
NADase activity by SARM1TIR requires E64232:11
Structural basis of NADase activity in SARM132:23
CryoEM structure of SARM1:1AD35:44
Model of SARM1 function37:13
Human SARM1TIR crystal structure37:36
NADase activities of plant TIR domains38:10
Cell death in plant leaves38:28
BB-loop mutant RUN1TIR(R64A+R65A) has increased NADase and HR activities39:11
TNL resistosome structures39:36
Comparison of TIR-domain arrangement in SARM1 and plant TNLs40:16
Crystal structure of AbTir TIR domain40:29
Stabilization of active structure with SARM1 inhibitor41:00
AbTir TIR domain: 3AD cryo-EM structure41:10
TLR adaptor and bacterial TIR domains form structurally analogous filaments41:57
Summary: TIR domain assemblies42:08
Mechanisms of regulation of TIR domain assembly43:09
TIR domains: self-association and enzymatic activity43:50
Summary: enzyme activities by TIR domains44:00
Conclusions44:38
Coworkers and collaborators46:00