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Structure and function of Toll/interleukin-1 receptor/resistance protein (TIR) domains

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Abstract

The Toll/interleukin-1 receptor/resistance protein (TIR) domain is a protein–protein interaction domain consisting of 125–200 residues, widely distributed in animals, plants and bacteria but absent from fungi, archea and viruses. In plants and animals, these domains are found in proteins with functions in innate immune pathways, while in bacteria, some TIR domain-containing proteins interfere with the innate immune pathways in the host. TIR domains function as protein scaffolds, mostly involving self-association and homotypic interactions with other TIR domains. In the last 15 years, the three-dimensional structures of TIR domains from several mammalian, plant and bacterial proteins have been reported. These structures, jointly with functional data including the identification of interacting proteins, have started to provide insight into the molecular basis of the assembly of animal and plant immune signaling complexes, and for host immunosuppression by bacterial pathogens. This review focuses on the current knowledge of the structures of the TIR domains and how the structure relates to function.

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Acknowledgments

The work in the authors’ laboratory was funded by the National Health and Medical Research Council (NHMRC, Australia; 1003326, 565526, 1071659) and the Australian Research Council (ARC; DP120100685). BK is an NHMRC Research Fellow (1003325).

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  1. School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, 4072, Australia

    Thomas Ve, Simon J. Williams & Bostjan Kobe

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  1. Thomas Ve
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  2. Simon J. Williams
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Correspondence to Bostjan Kobe.

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Thomas Ve and Simon J Williams are co-first authors

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Ve, T., Williams, S.J. & Kobe, B. Structure and function of Toll/interleukin-1 receptor/resistance protein (TIR) domains. Apoptosis 20, 250–261 (2015). https://doi.org/10.1007/s10495-014-1064-2

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