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6mb2

From Proteopedia

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Cryo-EM structure of the PYD filament of AIM2

6mb2, resolution 5.00Å

Structural highlights

6mb2 is a 30 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Experimental data:	Check to display Experimental Data
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] [GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.

Publication Abstract from PubMed

Absent in melanoma 2 (AIM2) is an essential cytosolic double-stranded DNA receptor that assembles with the adaptor, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 to form the AIM2 inflammasome, which leads to proteolytic maturation of cytokines and pyroptotic cell death. AIM2 contains an N-terminal Pyrin domain (PYD) that interacts with ASC through PYD/PYD interactions and nucleates ASC(PYD) filament formation. To elucidate the molecular basis of AIM2-induced ASC(PYD) polymerization, we generated AIM2(PYD) filaments fused to green fluorescent protein (GFP) and determined its cryo-electron microscopic (cryo-EM) structure. The map showed distinct definition of helices, allowing fitting of the crystal structure. Surprisingly, the GFP-AIM2(PYD) filament is a 1-start helix with helical parameters distinct from those of the 3-start ASC(PYD) filament. However, despite the apparent symmetry difference, helical net and detailed interface analyses reveal minimal changes in subunit packing. GFP-AIM2(PYD) nucleated ASC(PYD) filament formation in comparable efficiency as untagged AIM2(PYD), suggesting assembly plasticity in both AIM2(PYD) and ASC(PYD). The DNA-binding domain of AIM2 is able to form AIM2/DNA filaments, within which the AIM2(PYD) is brought into proximity to template ASC(PYD) filament assembly. Because ASC is able to interact with many PYD-containing receptors for the formation of inflammasomes, the observed structural plasticity may be critically important for this versatility in the PYD/PYD interactions.

Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2.,Lu A, Li Y, Yin Q, Ruan J, Yu X, Egelman E, Wu H Cell Discov. 2015;1. doi: 10.1038/celldisc.2015.13. Epub 2015 Jun 23. PMID:26583071^[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, Li Y, Yin Q, Ruan J, Yu X, Egelman E, Wu H. Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2. Cell Discov. 2015;1. doi: 10.1038/celldisc.2015.13. Epub 2015 Jun 23. PMID:26583071 doi:http://dx.doi.org/10.1038/celldisc.2015.13

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6mb2"

@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of the PYD filament of AIM2==
-<StructureSection load='6mb2' size='340' side='right' caption='[[6mb2]], [[Resolution|resolution]] 5.00&Aring;' scene=''>
+<SX load='6mb2' size='340' side='right' viewer='molstar' caption='[[6mb2]], [[Resolution|resolution]] 5.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mb2]] is a 30 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MB2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mb2]] is a 30 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MB2 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CRO:{2-[(1R,2R)-1-AMINO-2-HYDROXYPROPYL]-4-(4-HYDROXYBENZYLIDENE)-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>CRO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=6mb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb2 OCA], [http://pdbe.org/6mb2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb2 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb2 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6mb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb2 OCA], [http://pdbe.org/6mb2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb2 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 6mb2" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]]
 == References ==
 <references/>
 __TOC__
-</StructureSection>
+</SX>
+[[Category: Large Structures]]
 [[Category: Li, Y]]
 [[Category: Lu, A]]

6mb2

From Proteopedia

Current revision

Cryo-EM structure of the PYD filament of AIM2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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