| Structural highlights
Function
AIM2_MOUSE Involved in innate immune response by recognizing cytosolic double-stranded DNA and inducing caspase-1-activating inflammasome formation in macrophages. Upon binding to DNA is thought to undergo oligomerization and to associate with PYCARD initiating the recruitment of caspase-1 precusrsor and processing of interleukin-1 beta and interleukin-18. Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner. Can also trigger PYCARD-dependent, caspase-1-independent cell death that involves caspase-8.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The inflammasome is a key component of the innate immune system providing the initial defense against invading organisms. Failure of inflammasome formation is the main reason for many innate and acquired immune diseases. Cytosolic protein absent in melanoma 2 (AIM2) has been reported to play an essential role in double-stranded DNA (dsDNA) sensing and inflammasome formation in response to viruses or bacteria infection. The N-terminal pyrin domain (PYD) of AIM2 interacts with the ASC PYD domain, and then recruits downstream proteins to assemble the AIM2 inflammasome. The molecular mechanisms of PYD mediated signaling remain elusive as limited structural information on PYD family. Herein, we characterized the solution structure of mouse AIM2 PYD domain by NMR spectroscopy, and compared it with the crystal structures of its two human homologues. The comparison shows mAIM2 PYD adopts a unique alpha2-alpha3 helix conformation distinct from its human homologues, but similar to the pyrin domain of human NLRP10/PYNOD, which belongs to another family. In addition, the aggregation of mAIM2 PYD domain, with the increased salt concentration, reveals that both the charge surface and hydrophobic interaction play important roles in the self-association of mAIM2 PYD.
The NMR solution structure of AIM2 PYD domain from Mus musculus reveals a distinct alpha2-alpha3 helix conformation from its human homologues.,Hou X, Niu X Biochem Biophys Res Commun. 2015 May 29;461(2):396-400. doi:, 10.1016/j.bbrc.2015.04.046. Epub 2015 Apr 16. PMID:25888795[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E, Fitzgerald KA. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 2009 Mar 26;458(7237):514-8. doi: 10.1038/nature07725. Epub 2009 Jan 21. PMID:19158675 doi:10.1038/nature07725
- ↑ Roberts TL, Idris A, Dunn JA, Kelly GM, Burnton CM, Hodgson S, Hardy LL, Garceau V, Sweet MJ, Ross IL, Hume DA, Stacey KJ. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science. 2009 Feb 20;323(5917):1057-60. doi: 10.1126/science.1169841. Epub 2009, Jan 8. PMID:19131592 doi:10.1126/science.1169841
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- ↑ Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, Wu J, Datta P, McCormick M, Huang L, McDermott E, Eisenlohr L, Landel CP, Alnemri ES. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol. 2010 May;11(5):385-93. doi: 10.1038/ni.1859. Epub 2010 Mar 28. PMID:20351693 doi:10.1038/ni.1859
- ↑ Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E, Hornung V, Vogel SN, Szomolanyi-Tsuda E, Fitzgerald KA. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol. 2010 May;11(5):395-402. doi: 10.1038/ni.1864. Epub 2010 Mar 28. PMID:20351692 doi:10.1038/ni.1864
- ↑ Jones JW, Kayagaki N, Broz P, Henry T, Newton K, O'Rourke K, Chan S, Dong J, Qu Y, Roose-Girma M, Dixit VM, Monack DM. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9771-6. doi:, 10.1073/pnas.1003738107. Epub 2010 May 10. PMID:20457908 doi:10.1073/pnas.1003738107
- ↑ Pierini R, Juruj C, Perret M, Jones CL, Mangeot P, Weiss DS, Henry T. AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. Cell Death Differ. 2012 Oct;19(10):1709-21. doi: 10.1038/cdd.2012.51. Epub 2012, May 4. PMID:22555457 doi:10.1038/cdd.2012.51
- ↑ Belhocine K, Monack DM. Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells. Cell Microbiol. 2012 Jan;14(1):71-80. doi: 10.1111/j.1462-5822.2011.01700.x. Epub, 2011 Oct 17. PMID:21902795 doi:10.1111/j.1462-5822.2011.01700.x
- ↑ Hou X, Niu X. The NMR solution structure of AIM2 PYD domain from Mus musculus reveals a distinct alpha2-alpha3 helix conformation from its human homologues. Biochem Biophys Res Commun. 2015 May 29;461(2):396-400. doi:, 10.1016/j.bbrc.2015.04.046. Epub 2015 Apr 16. PMID:25888795 doi:http://dx.doi.org/10.1016/j.bbrc.2015.04.046
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