Structure and function of the SPRY/B30.2 domain proteins involved in innate immunity

Authors

  • Akshay A. D'Cruz,

    1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medical Biology of the University of Melbourne, Parkville, Victoria, Australia
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  • Jeffrey J. Babon,

    1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medical Biology of the University of Melbourne, Parkville, Victoria, Australia
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  • Raymond S. Norton,

    1. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
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  • Nicos A. Nicola,

    1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medical Biology of the University of Melbourne, Parkville, Victoria, Australia
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  • Sandra E. Nicholson

    Corresponding author
    1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medical Biology of the University of Melbourne, Parkville, Victoria, Australia
    • Inflammation Division, The Walter and Eliza Hall Institute, 1G Royal Pde, Parkville, Victoria, 3052, Australia
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Abstract

The SPRY domain is a protein interaction module found in 77 murine and ∼100 human proteins, and is implicated in important biological pathways, including those that regulate innate and adaptive immunity. The current definition of the SPRY domain is based on a sequence repeat discovered in the splA kinase and ryanodine receptors. The greater SPRY family is divided into the B30.2 (which contains a PRY extension at the N-terminus) and “SPRY-only” sub-families. In this brief review, we examine the current structural and biochemical literature on SPRY/B30.2 domain involvement in key immune processes and highlight a PRY-like 60 amino acid region in the N-terminus of “SPRY-only” proteins. Phylogenetic, structural, and functional analyses suggest that this N-terminal region is related to the PRY region of B30.2 and should be characterized as part of an extended SPRY domain. Greater understanding of the functional importance of the N-terminal region in “SPRY only” proteins will enhance our ability to interrogate SPRY interactions with their respective binding partners.

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