4o7q
From Proteopedia
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| - | + | ==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]] 1.82Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <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> | |
| - | ==Function== | + | </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> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://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> | [[http://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 == | ||
| + | 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<ref>PMID:24406744</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| - | [[Category: Kabaleeswaran, V | + | [[Category: Kabaleeswaran, V]] |
| - | [[Category: Lu, A | + | [[Category: Lu, A]] |
| - | [[Category: Wu, H | + | [[Category: Wu, H]] |
[[Category: Apoptosis]] | [[Category: Apoptosis]] | ||
[[Category: Inflammasome]] | [[Category: Inflammasome]] | ||
Revision as of 12:57, 25 December 2014
Crystal Structure of the F27G AIM2 Pyrin Domain Mutant and Similarities of its Self-association to DED/DED Interactions
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Categories: Human | Kabaleeswaran, V | Lu, A | Wu, H | Apoptosis | Inflammasome | Pyd/dd | Signal transduction | Signaling protein
