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3j6c

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Revision as of 19:11, 4 August 2016

Cryo-EM structure of MAVS CARD filament

Structural highlights

3j6c 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:	MAVS, IPS1, KIAA1271, VISA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MAVS_HUMAN] Required for innate immune defense against viruses. Acts downstream of DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Mitochondrial antiviral signaling (MAVS) protein is required for innate immune responses against RNA viruses. In virus-infected cells MAVS forms prion-like aggregates to activate antiviral signaling cascades, but the underlying structural mechanism is unknown. Here we report cryo-electron microscopic structures of the helical filaments formed by both the N-terminal caspase activation and recruitment domain (CARD) of MAVS and a truncated MAVS lacking part of the proline-rich region and the C-terminal transmembrane domain. Both structures are left-handed three-stranded helical filaments, revealing specific interfaces between individual CARD subunits that are dictated by electrostatic interactions between neighboring strands and hydrophobic interactions within each strand. Point mutations at multiple locations of these two interfaces impaired filament formation and antiviral signaling. Super-resolution imaging of virus-infected cells revealed rod-shaped MAVS clusters on mitochondria. These results elucidate the structural mechanism of MAVS polymerization, and explain how an alpha-helical domain uses distinct chemical interactions to form self-perpetuating filaments. DOI: http://dx.doi.org/10.7554/eLife.01489.001.

Structural basis for the prion-like MAVS filaments in antiviral innate immunity.,Xu H, He X, Zheng H, Huang LJ, Hou F, Yu Z, de la Cruz MJ, Borkowski B, Zhang X, Chen ZJ, Jiang QX Elife. 2014 Jan 1;3:e01489. doi: 10.7554/eLife.01489. PMID:24569476^[7]

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

References

↑ Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005 Sep 9;122(5):669-82. PMID:16125763 doi:10.1016/j.cell.2005.08.012
↑ Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005 Sep 16;19(6):727-40. PMID:16153868 doi:S1097-2765(05)01556-X
↑ Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005 Oct 20;437(7062):1167-72. Epub 2005 Sep 21. PMID:16177806 doi:nature04193
↑ Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005 Oct;6(10):981-8. Epub 2005 Aug 28. PMID:16127453 doi:10.1038/ni1243
↑ Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009 Aug 7;138(3):576-91. doi: 10.1016/j.cell.2009.06.015. Epub 2009 Jul, 23. PMID:19631370 doi:10.1016/j.cell.2009.06.015
↑ Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC. Peroxisomes are signaling platforms for antiviral innate immunity. Cell. 2010 May 14;141(4):668-81. doi: 10.1016/j.cell.2010.04.018. Epub 2010 May, 6. PMID:20451243 doi:10.1016/j.cell.2010.04.018
↑ Xu H, He X, Zheng H, Huang LJ, Hou F, Yu Z, de la Cruz MJ, Borkowski B, Zhang X, Chen ZJ, Jiang QX. Structural basis for the prion-like MAVS filaments in antiviral innate immunity. Elife. 2014 Jan 1;3:e01489. doi: 10.7554/eLife.01489. PMID:24569476

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3j6c"

@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of MAVS CARD filament==
 <StructureSection load='3j6c' size='340' side='right' caption='[[3j6c]], [[Resolution|resolution]] 9.60&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[3j6c]] 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=3J6C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J6C FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAVS, IPS1, KIAA1271, VISA ([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=3j6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j6c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3j6c RCSB], [http://www.ebi.ac.uk/pdbsum/3j6c 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=3j6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j6c OCA], [http://pdbe.org/3j6c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j6c RCSB], [http://www.ebi.ac.uk/pdbsum/3j6c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j6c 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 3j6c" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3j6c

From Proteopedia

Revision as of 19:11, 4 August 2016

Cryo-EM structure of MAVS CARD filament

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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