4o7q

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Revision as of 20:38, 4 August 2016

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 Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	AIM2 (HUMAN)
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]

Publication Abstract from PubMed

Absent in melanoma 2 (AIM2) is a cytoplasmic double-stranded DNA sensor involved in innate immunity. It uses its C-terminal HIN domain for recognizing double-stranded DNA and its N-terminal pyrin domain (PYD) for eliciting downstream effects through recruitment and activation of apoptosis-associated Speck-like protein containing CARD (ASC). ASC in turn recruits caspase-1 and/or caspase-11 to form the AIM2 inflammasome. The activated caspases process proinflammatory cytokines IL-1beta and IL-18 and induce the inflammatory form of cell death pyroptosis. Here we show that AIM PYD (AIM2PYD) self-oligomerizes. We notice significant sequence homology of AIM2PYD with the hydrophobic patches of death effector domain (DED)-containing proteins and confirm that mutations on these residues disrupt AIM2PYD self-association. The crystal structure at 1.82A resolution of such a mutant, F27G of AIM2PYD, shows the canonical six-helix (H1-H6) bundle fold in the death domain superfamily. In contrast to the wild-type AIM2PYD structure crystallized in fusion with the large maltose-binding protein tag, the H2-H3 region of the AIM2PYD F27G is well defined with low B-factors. Structural analysis shows that the conserved hydrophobic patches engage in a type I interaction that has been observed in DED/DED and other death domain superfamily interactions. While previous mutagenesis studies of PYDs point to the involvement of charged interactions, our results reveal the importance of hydrophobic interactions in the same interfaces. These centrally localized hydrophobic residues within fairly charged patches may form the hot spots in AIM2PYD self-association and may represent a common mode of PYD/PYD interactions in general.

Crystal Structure of the F27G AIM2 PYD Mutant and Similarities of Its Self-Association to DED/DED Interactions.,Lu A, Kabaleeswaran V, Fu T, Magupalli VG, Wu H J Mol Biol. 2014 Jan 7. pii: S0022-2836(13)00816-4. doi:, 10.1016/j.jmb.2013.12.029. PMID:24406744^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Lu A, Kabaleeswaran V, Fu T, Magupalli VG, Wu H. Crystal Structure of the F27G AIM2 PYD Mutant and Similarities of Its Self-Association to DED/DED Interactions. J Mol Biol. 2014 Jan 7. pii: S0022-2836(13)00816-4. doi:, 10.1016/j.jmb.2013.12.029. PMID:24406744 doi:http://dx.doi.org/10.1016/j.jmb.2013.12.029

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

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OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o7q"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the F27G AIM2 Pyrin Domain Mutant and Similarities of its Self-association to DED/DED Interactions==
 <StructureSection load='4o7q' size='340' side='right' caption='[[4o7q]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4o7q]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O7Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O7Q FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AIM2 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o7q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o7q RCSB], [http://www.ebi.ac.uk/pdbsum/4o7q PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o7q OCA], [http://pdbe.org/4o7q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o7q RCSB], [http://www.ebi.ac.uk/pdbsum/4o7q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o7q ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4o7q" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4o7q

From Proteopedia

Revision as of 20:38, 4 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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