4z8m

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the MAVS-TRAF6 complex

Structural highlights

4z8m is a 4 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:	X-ray diffraction, Resolution 2.95Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRAF6_HUMAN E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Publication Abstract from PubMed

In response to viral infection, cytosolic retinoic acid-inducible gene I-like receptors sense viral RNA and promote oligomerization of mitochondrial antiviral signaling protein (MAVS), which then recruits tumor necrosis factor receptor-associated factor (TRAF) family proteins, including TRAF6, to activate an antiviral response. Currently, the interaction between MAVS and TRAF6 is only partially understood, and atomic details are lacking. Here, we demonstrated that MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2 (T6BM2; amino acids 455-460). Further, we solved the crystal structure of MAVS T6BM2 in complex with the TRAF6 TRAF_C domain at 2.95 A resolution. T6BM2 of MAVS binds to the canonical adaptor-binding groove of the TRAF_C domain. Structure-directed mutational analyses in vitro and in cells revealed that MAVS binding to TRAF6 via T6BM2 instead of T6BM1 is essential but not sufficient for an optimal antiviral response. Particularly, a MAVS mutant Y460E retained its TRAF6-binding ability as predicted but showed significantly impaired signaling activity, highlighting the functional importance of this tyrosine. Moreover, these observations were further confirmed in MAVS(-/-) mouse embryonic fibroblast cells. Collectively, our work provides a structural basis for understanding the MAVS-TRAF6 antiviral response.

Structural Insights into Mitochondrial Antiviral Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Signaling.,Shi Z, Zhang Z, Zhang Z, Wang Y, Li C, Wang X, He F, Sun L, Jiao S, Shi W, Zhou Z J Biol Chem. 2015 Oct 30;290(44):26811-20. doi: 10.1074/jbc.M115.666578. Epub, 2015 Sep 18. PMID:26385923^[11]

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

References

↑ Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV. TRAF6 is a signal transducer for interleukin-1. Nature. 1996 Oct 3;383(6599):443-6. PMID:8837778 doi:10.1038/383443a0
↑ Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000 Oct 13;103(2):351-61. PMID:11057907
↑ Wang Y, Tang Y, Teng L, Wu Y, Zhao X, Pei G. Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2006 Feb;7(2):139-47. Epub 2005 Dec 25. PMID:16378096 doi:10.1038/ni1294
↑ Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG. Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. J Biol Chem. 2007 Feb 9;282(6):4102-12. Epub 2006 Nov 29. PMID:17135271 doi:10.1074/jbc.M609503200
↑ Pham LV, Zhou HJ, Lin-Lee YC, Tamayo AT, Yoshimura LC, Fu L, Darnay BG, Ford RJ. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. J Biol Chem. 2008 Feb 22;283(8):5081-9. Epub 2007 Dec 19. PMID:18093978 doi:10.1074/jbc.M706307200
↑ Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landstrom M. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol. 2008 Oct;10(10):1199-207. doi: 10.1038/ncb1780. Epub 2008 Aug 31. PMID:18758450 doi:10.1038/ncb1780
↑ Xia ZP, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, Zeng W, Chen ZJ. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 2009 Sep 3;461(7260):114-9. doi: 10.1038/nature08247. Epub 2009 Aug 12. PMID:19675569 doi:10.1038/nature08247
↑ Yang WL, Wang J, Chan CH, Lee SW, Campos AD, Lamothe B, Hur L, Grabiner BC, Lin X, Darnay BG, Lin HK. The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science. 2009 Aug 28;325(5944):1134-8. doi: 10.1126/science.1175065. PMID:19713527 doi:10.1126/science.1175065
↑ Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, Segal D, Dzivenu OK, Vologodskaia M, Yim M, Du K, Singh S, Pike JW, Darnay BG, Choi Y, Wu H. Distinct molecular mechanism for initiating TRAF6 signalling. Nature. 2002 Jul 25;418(6896):443-7. PMID:12140561 doi:10.1038/nature00888
↑ Yin Q, Lin SC, Lamothe B, Lu M, Lo YC, Hura G, Zheng L, Rich RL, Campos AD, Myszka DG, Lenardo MJ, Darnay BG, Wu H. E2 interaction and dimerization in the crystal structure of TRAF6. Nat Struct Mol Biol. 2009 Jun;16(6):658-66. Epub 2009 May 24. PMID:19465916 doi:10.1038/nsmb.1605
↑ Shi Z, Zhang Z, Zhang Z, Wang Y, Li C, Wang X, He F, Sun L, Jiao S, Shi W, Zhou Z. Structural Insights into Mitochondrial Antiviral Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Signaling. J Biol Chem. 2015 Oct 30;290(44):26811-20. doi: 10.1074/jbc.M115.666578. Epub, 2015 Sep 18. PMID:26385923 doi:http://dx.doi.org/10.1074/jbc.M115.666578

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/4z8m"

Categories: Homo sapiens | Large Structures | Shi ZB | Zhou Z

@@ Line 1: / Line 1: @@
 ==Crystal structure of the MAVS-TRAF6 complex==
-<StructureSection load='4z8m' size='340' side='right' caption='[[4z8m]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
+<StructureSection load='4z8m' size='340' side='right'caption='[[4z8m]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4z8m]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z8M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z8M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4z8m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z8M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z8M FirstGlance]. <br>
-</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=4z8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z8m OCA], [http://pdbe.org/4z8m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z8m RCSB], [http://www.ebi.ac.uk/pdbsum/4z8m PDBsum]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4z8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z8m OCA], [https://pdbe.org/4z8m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z8m RCSB], [https://www.ebi.ac.uk/pdbsum/4z8m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z8m ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TRAF6_HUMAN TRAF6_HUMAN]] E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.<ref>PMID:8837778</ref> <ref>PMID:11057907</ref> <ref>PMID:16378096</ref> <ref>PMID:17135271</ref> <ref>PMID:18093978</ref> <ref>PMID:18758450</ref> <ref>PMID:19675569</ref> <ref>PMID:19713527</ref> <ref>PMID:12140561</ref> <ref>PMID:19465916</ref>  [[http://www.uniprot.org/uniprot/MAVS_HUMAN 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.<ref>PMID:16125763</ref> <ref>PMID:16153868</ref> <ref>PMID:16177806</ref> <ref>PMID:16127453</ref> <ref>PMID:19631370</ref> <ref>PMID:20451243</ref>
+[https://www.uniprot.org/uniprot/TRAF6_HUMAN TRAF6_HUMAN] E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.<ref>PMID:8837778</ref> <ref>PMID:11057907</ref> <ref>PMID:16378096</ref> <ref>PMID:17135271</ref> <ref>PMID:18093978</ref> <ref>PMID:18758450</ref> <ref>PMID:19675569</ref> <ref>PMID:19713527</ref> <ref>PMID:12140561</ref> <ref>PMID:19465916</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 18: @@
 </div>
 <div class="pdbe-citations 4z8m" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Shi, Z B]]
+[[Category: Homo sapiens]]
-[[Category: Zhou, Z]]
+[[Category: Large Structures]]
-[[Category: Adaptor]]
+[[Category: Shi ZB]]
-[[Category: Antiviral signaling]]
+[[Category: Zhou Z]]
-[[Category: Complex]]
-[[Category: E3 ligase]]
-[[Category: Ligase-signaling protein complex]]

4z8m

From Proteopedia

Current revision

Crystal structure of the MAVS-TRAF6 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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