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4o7q

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Crystal Structure of the F27G AIM2 Pyrin Domain Mutant and Similarities of its Self-association to DED/DED Interactions

Structural highlights

4o7q is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.82Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AIM2_HUMAN 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 (By similarity). Tumor suppressor which may act by repressing NF-kappa-B transcriptional activity.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Chen IF, Ou-Yang F, Hung JY, Liu JC, Wang H, Wang SC, Hou MF, Hortobagyi GN, Hung MC. AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model. Mol Cancer Ther. 2006 Jan;5(1):1-7. PMID:16432157 doi:http://dx.doi.org/10.1158/1535-7163.MCT-05-0310
↑ Woerner SM, Kloor M, Schwitalle Y, Youmans H, Doeberitz Mv, Gebert J, Dihlmann S. The putative tumor suppressor AIM2 is frequently affected by different genetic alterations in microsatellite unstable colon cancers. Genes Chromosomes Cancer. 2007 Dec;46(12):1080-9. PMID:17726700 doi:http://dx.doi.org/10.1002/gcc.20493
↑ Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett KL, Superti-Furga G. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol. 2009 Mar;10(3):266-72. doi: 10.1038/ni.1702. Epub 2009 Jan 21. PMID:19158679 doi:http://dx.doi.org/10.1038/ni.1702
↑ Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 2009 Mar 26;458(7237):509-13. doi: 10.1038/nature07710. Epub 2009 Jan 21. PMID:19158676 doi:10.1038/nature07710
↑ 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
↑ Tsuchiya K, Hara H, Kawamura I, Nomura T, Yamamoto T, Daim S, Dewamitta SR, Shen Y, Fang R, Mitsuyama M. Involvement of absent in melanoma 2 in inflammasome activation in macrophages infected with Listeria monocytogenes. J Immunol. 2010 Jul 15;185(2):1186-95. doi: 10.4049/jimmunol.1001058. Epub 2010, Jun 21. PMID:20566831 doi:http://dx.doi.org/10.4049/jimmunol.1001058