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SMOCs: supramolecular organizing centres that control innate immunity

Nature Reviews Immunology volume 14, pages 821–826 (2014)Cite this article

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Abstract

The diverse receptor families of the innate immune system activate signal transduction pathways that are important for host defence, but common themes to explain the operation of these pathways remain undefined. In this Opinion article, we propose — on the basis of recent structural and cell biological studies — the concept of supramolecular organizing centres (SMOCs) as location-specific higher-order signalling complexes in which increased local concentrations of signalling components promote the intrinsically weak allosteric interactions that are required for enzyme activation. We suggest that SMOCs are assembled on various membrane-bound organelles or other intracellular sites, which may assist signal amplification to reach a response threshold and potentially define the specificity of cellular responses that are induced in response to infectious and non-infectious insults.

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Figure 1: SMOC formation for TLRs, RLRs and NLRs.
Figure 2: Structures of SMOCs that are formed by the mechanism of nucleated polymerization.

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Change history

  • 03 November 2014

    In Figure 1 of the original version of this article, the Toll-like receptor within the endosome was incorrectly labelled as TLR4. This should have been labelled as TLR9 and has now been corrected online. Nature Reviews Immunology apologizes for this error.

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Acknowledgements

J.C.K. is supported by the US National Institutes of Health (NIH; grants AI093589, AI072955 and AI113141-01) and an unrestricted gift from Mead Johnson & Company. J.C.K. holds an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. H.W. is supported by NIH and the Asa and Patricia Springer Professorship of the Harvard Medical School.

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  1. Boston Children's Hospital and Harvard Medical School, Boston, 02446, Massachusetts, USA

    Jonathan C. Kagan, Venkat Giri Magupalli & Hao Wu

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  1. Jonathan C. Kagan
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Correspondence to Jonathan C. Kagan or Hao Wu.

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Kagan, J., Magupalli, V. & Wu, H. SMOCs: supramolecular organizing centres that control innate immunity. Nat Rev Immunol 14, 821–826 (2014). https://doi.org/10.1038/nri3757

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