|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3rn5' size='340' side='right'caption='[[3rn5]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='3rn5' size='340' side='right'caption='[[3rn5]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rn5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RN5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rn5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RN5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rn2|3rn2]], [[3rlo|3rlo]], [[3rln|3rln]], [[3rnu|3rnu]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AIM2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rn5 OCA], [https://pdbe.org/3rn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rn5 RCSB], [https://www.ebi.ac.uk/pdbsum/3rn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rn5 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rn5 OCA], [https://pdbe.org/3rn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rn5 RCSB], [https://www.ebi.ac.uk/pdbsum/3rn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rn5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/AIM2_HUMAN 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.<ref>PMID:16432157</ref> <ref>PMID:17726700</ref> <ref>PMID:19158679</ref> <ref>PMID:19158676</ref> <ref>PMID:19158675</ref> <ref>PMID:20566831</ref>
| + | [https://www.uniprot.org/uniprot/AIM2_HUMAN 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.<ref>PMID:16432157</ref> <ref>PMID:17726700</ref> <ref>PMID:19158679</ref> <ref>PMID:19158676</ref> <ref>PMID:19158675</ref> <ref>PMID:20566831</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.
| + | |
| - | | + | |
| - | Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor.,Jin T, Perry A, Jiang J, Smith P, Curry JA, Unterholzner L, Jiang Z, Horvath G, Rathinam VA, Johnstone RW, Hornung V, Latz E, Bowie AG, Fitzgerald KA, Xiao TS Immunity. 2012 Apr 20;36(4):561-71. Epub 2012 Apr 5. PMID:22483801<ref>PMID:22483801</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3rn5" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jin, T C]] | + | [[Category: Jin TC]] |
| - | [[Category: Xiao, T]] | + | [[Category: Xiao T]] |
| - | [[Category: Cytosolic]]
| + | |
| - | [[Category: Dna binding]]
| + | |
| - | [[Category: Immune system-dna complex]]
| + | |
| - | [[Category: Ob fold]]
| + | |
| Structural highlights
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
|
