3j6j | pdb_00003j6j

3.6 Angstrom resolution MAVS filament generated from helical reconstruction

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Structural highlights

3j6j is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.64Å
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

RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARDMAVS), and requires its interaction with the tandem CARDs of RIG-I (2CARDRIG-I). However, the precise nature of the interaction between 2CARDRIG-I and CARDMAVS, and how this interaction leads to CARDMAVS filament assembly, has been unclear. Here we report a 3.6 A electron microscopy structure of the CARDMAVS filament and a 3.4 A crystal structure of the 2CARDRIG-I:CARDMAVS complex, representing 2CARDRIG-I "caught in the act" of nucleating the CARDMAVS filament. These structures, together with functional analyses, show that 2CARDRIG-I acts as a template for the CARDMAVS filament assembly, by forming a helical tetrameric structure and recruiting CARDMAVS along its helical trajectory. Our work thus reveals that signal activation by RIG-I occurs by imprinting its helical assembly architecture on MAVS, a previously uncharacterized mechanism of signal transmission.

Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I.,Wu B, Peisley A, Tetrault D, Li Z, Egelman EH, Magor KE, Walz T, Penczek PA, Hur S Mol Cell. 2014 Jul 9. pii: S1097-2765(14)00492-4. doi:, 10.1016/j.molcel.2014.06.010. PMID:25018021^[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
↑ Wu B, Peisley A, Tetrault D, Li Z, Egelman EH, Magor KE, Walz T, Penczek PA, Hur S. Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I. Mol Cell. 2014 Jul 9. pii: S1097-2765(14)00492-4. doi:, 10.1016/j.molcel.2014.06.010. PMID:25018021 doi:https://dx.doi.org/10.1016/j.molcel.2014.06.010

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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] Wu B, Peisley A, Tetrault D, Li Z, Egelman EH, Magor KE, Walz T, Penczek PA, Hur S. Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I. Mol Cell. 2014 Jul 9. pii: S1097-2765(14)00492-4. doi:, 10.1016/j.molcel.2014.06.010. PMID:25018021 doi:https://dx.doi.org/10.1016/j.molcel.2014.06.010

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3j6j | pdb_00003j6j

3.6 Angstrom resolution MAVS filament generated from helical reconstruction

Structural highlights

Function

Publication Abstract from PubMed

References

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