BibTex format

author = {Carlsson, E and Ding, JL and Byrne, B},
doi = {10.1016/j.bbamcr.2015.11.021},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},
pages = {244--253},
title = {SARM modulates MyD88-mediated TLR activation through BB-loop dependent TIR-TIR interactions.},
url = {},
volume = {1863},
year = {2015}

RIS format (EndNote, RefMan)

AB - Toll-like receptors (TLRs) recognise invading pathogens and initiate an innate immune response by recruiting intracellular adaptor proteins via heterotypic Toll/interleukin-1 receptor (TIR) domain interactions. Of the five TIR domain-containing adaptor proteins identified, Sterile α- and armadillo-motif-containing protein (SARM) is functionally unique; suppressing immune signalling instead of promoting it. Here we demonstrate that the recombinantly expressed and purified SARM TIR domain interacts with both the major human TLR adaptors, MyD88 and TRIF. A single glycine residue located in the BB-loop of the SARM TIR domain, G601, was identified as essential for interaction. A short peptide derived from this domain was also found to interact with MyD88 in vitro. SARM expression in HEK-293 cells was found to significantly suppress lipopolysaccharide (LPS)-mediated upregulation of inflammatory cytokines, IL-8 and TNF-α, an effect lost in the G601A mutant. The same result was observed with cytokine activation initiated by MyD88 expression and stimulation of TLR2 with lipoteichoic acid (LTA), suggesting that SARM is capable of suppressing both TRIF- and MyD88- dependent TLR signalling. Our findings indicate that SARM acts on a broader set of target proteins than previously thought, and that the BB-loop motif is functionally important, giving further insight into the endogenous mechanisms used to suppress inflammation in immune cells.
AU - Carlsson,E
AU - Ding,JL
AU - Byrne,B
DO - 10.1016/j.bbamcr.2015.11.021
EP - 253
PY - 2015///
SN - 0167-4889
SP - 244
TI - SARM modulates MyD88-mediated TLR activation through BB-loop dependent TIR-TIR interactions.
T2 - Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
UR -
UR -
VL - 1863
ER -