The functional and structural role of cysteine residues in Toll-like receptor signalling adaptor MAL/ TIRAP — ASN Events
  1. Schedule
  2. Session Five - Poster Session A including Refreshments
  3. The functional and structural role of cysteine residues in Toll-like receptor signalling adaptor MAL/ TIRAP

The functional and structural role of cysteine residues in Toll-like receptor signalling adaptor MAL/ TIRAP (#128)

Peter Lavrencic 1 2 3 4 , Thomas Ve 2 4 5 , Mehdi Mobli 1 4 5 , Bostjan Kobe 1 2 3 4
  1. Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia
  2. Australian Infections Disease Research Centre, The University of Queensland, Brisbane, QLD, Australia
  3. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
  4. Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
  5. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Austraila

MyD88 adaptor protein (MAL) / TIR domain-containing adaptor protein (TIRAP) is a key player in the Toll-like receptor (TLR) signalling cascade of the human immune system. As the TLRs are stimulated, the Toll/ interleukin-1 receptor (TIR) domain of MAL binds to the intracellular domain of the TLR to relay the signal to MyD88 and in turn activate the production of NF-kB and cytokines.

Our group recently solved the crystal structure of MAL, which showed that specific cysteines formed two disulphide bonds that could contribute to the stability of the protein1. Following NMR sequential protein backbone assignment, data revealed that the protein contained four reduced cysteine residues in solution. In addition, another two cysteine residues appear to be reactive and may be involved in redox-regulated binding and signal transduction. Future work will be focused on the functional role of cysteines in the MAL protein.

TIR domains have been shown to become active when they form dimers. A stable dimer of the MAL TIR domain has been purified and confirmed using both small angle laser scattering and multi angle light scattering. Future work will focus on crystallising the MAL TIR-domain dimer to reveal the interacting interface and the possible functional significance of the dimer form.