1ca4: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='1ca4' size='340' side='right'caption='[[1ca4]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='1ca4' size='340' side='right'caption='[[1ca4]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1ca4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CA4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1ca4]] is a 6 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=1CA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CA4 FirstGlance]. <br>
</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=1ca4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ca4 OCA], [https://pdbe.org/1ca4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ca4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ca4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ca4 ProSAT]</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]] 2.2&#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=1ca4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ca4 OCA], [https://pdbe.org/1ca4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ca4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ca4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ca4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/TRAF2_HUMAN TRAF2_HUMAN]] Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain.<ref>PMID:10346818</ref> <ref>PMID:11907583</ref> <ref>PMID:12917689</ref> <ref>PMID:15383523</ref> <ref>PMID:19506082</ref> <ref>PMID:19150425</ref> <ref>PMID:18981220</ref> <ref>PMID:19918265</ref> <ref>PMID:20064526</ref> <ref>PMID:19937093</ref> <ref>PMID:20047764</ref> <ref>PMID:20577214</ref> <ref>PMID:19810754</ref> <ref>PMID:20385093</ref>
[https://www.uniprot.org/uniprot/TRAF2_HUMAN TRAF2_HUMAN] Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain.<ref>PMID:10346818</ref> <ref>PMID:11907583</ref> <ref>PMID:12917689</ref> <ref>PMID:15383523</ref> <ref>PMID:19506082</ref> <ref>PMID:19150425</ref> <ref>PMID:18981220</ref> <ref>PMID:19918265</ref> <ref>PMID:20064526</ref> <ref>PMID:19937093</ref> <ref>PMID:20047764</ref> <ref>PMID:20577214</ref> <ref>PMID:19810754</ref> <ref>PMID:20385093</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 34: Line 35:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Burkitt, V]]
[[Category: Burkitt V]]
[[Category: Park, Y C]]
[[Category: Park YC]]
[[Category: Tong, L]]
[[Category: Tong L]]
[[Category: Villa, A R]]
[[Category: Villa AR]]
[[Category: Wu, H]]
[[Category: Wu H]]
[[Category: Adapter protein]]
[[Category: Cell survival]]
[[Category: Tnf signaling]]
[[Category: Traf]]

Latest revision as of 02:25, 28 December 2023

STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 (TRAF2)STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 (TRAF2)

Structural highlights

1ca4 is a 6 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 2.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRAF2_HUMAN Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands.

Structural basis for self-association and receptor recognition of human TRAF2.,Park YC, Burkitt V, Villa AR, Tong L, Wu H Nature. 1999 Apr 8;398(6727):533-8. PMID:10206649[15]

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

See Also

References

  1. ↑ Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev. 1999 May 15;13(10):1297-308. PMID:10346818
  2. ↑ Li X, Yang Y, Ashwell JD. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature. 2002 Mar 21;416(6878):345-7. PMID:11907583 doi:10.1038/416345a
  3. ↑ Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G. CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature. 2003 Aug 14;424(6950):793-6. PMID:12917689 doi:http://dx.doi.org/10.1038/nature01803
  4. ↑ He L, Grammer AC, Wu X, Lipsky PE. TRAF3 forms heterotrimers with TRAF2 and modulates its ability to mediate NF-{kappa}B activation. J Biol Chem. 2004 Dec 31;279(53):55855-65. Epub 2004 Sep 21. PMID:15383523 doi:10.1074/jbc.M407284200
  5. ↑ Csomos RA, Brady GF, Duckett CS. Enhanced cytoprotective effects of the inhibitor of apoptosis protein cellular IAP1 through stabilization with TRAF2. J Biol Chem. 2009 Jul 31;284(31):20531-9. doi: 10.1074/jbc.M109.029983. Epub 2009, Jun 8. PMID:19506082 doi:10.1074/jbc.M109.029983
  6. ↑ Li S, Wang L, Dorf ME. PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination. Mol Cell. 2009 Jan 16;33(1):30-42. doi: 10.1016/j.molcel.2008.11.023. PMID:19150425 doi:10.1016/j.molcel.2008.11.023
  7. ↑ Blackwell K, Zhang L, Thomas GS, Sun S, Nakano H, Habelhah H. TRAF2 phosphorylation modulates tumor necrosis factor alpha-induced gene expression and cell resistance to apoptosis. Mol Cell Biol. 2009 Jan;29(2):303-14. doi: 10.1128/MCB.00699-08. Epub 2008 Nov 3. PMID:18981220 doi:10.1128/MCB.00699-08
  8. ↑ Sondarva G, Kundu CN, Mehrotra S, Mishra R, Rangasamy V, Sathyanarayana P, Ray RS, Rana B, Rana A. TRAF2-MLK3 interaction is essential for TNF-alpha-induced MLK3 activation. Cell Res. 2010 Jan;20(1):89-98. doi: 10.1038/cr.2009.125. Epub 2009 Nov 17. PMID:19918265 doi:10.1038/cr.2009.125
  9. ↑ Zhang L, Blackwell K, Shi Z, Habelhah H. The RING domain of TRAF2 plays an essential role in the inhibition of TNFalpha-induced cell death but not in the activation of NF-kappaB. J Mol Biol. 2010 Feb 26;396(3):528-39. doi: 10.1016/j.jmb.2010.01.008. Epub 2010 , Jan 11. PMID:20064526 doi:10.1016/j.jmb.2010.01.008
  10. ↑ Li S, Lu K, Wang J, An L, Yang G, Chen H, Cui Y, Yin X, Xie P, Xing G, He F, Zhang L. Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Mol Cell Biochem. 2010 May;338(1-2):11-7. doi: 10.1007/s11010-009-0315-y. Epub, 2009 Nov 24. PMID:19937093 doi:10.1007/s11010-009-0315-y
  11. ↑ Sasai M, Tatematsu M, Oshiumi H, Funami K, Matsumoto M, Hatakeyama S, Seya T. Direct binding of TRAF2 and TRAF6 to TICAM-1/TRIF adaptor participates in activation of the Toll-like receptor 3/4 pathway. Mol Immunol. 2010 Mar;47(6):1283-91. doi: 10.1016/j.molimm.2009.12.002. Epub 2010, Jan 4. PMID:20047764 doi:10.1016/j.molimm.2009.12.002
  12. ↑ Alvarez SE, Harikumar KB, Hait NC, Allegood J, Strub GM, Kim EY, Maceyka M, Jiang H, Luo C, Kordula T, Milstien S, Spiegel S. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature. 2010 Jun 24;465(7301):1084-8. doi: 10.1038/nature09128. PMID:20577214 doi:10.1038/nature09128
  13. ↑ Yin Q, Lamothe B, Darnay BG, Wu H. Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry. 2009 Nov 10;48(44):10558-67. PMID:19810754 doi:10.1021/bi901462e
  14. ↑ Zheng C, Kabaleeswaran V, Wang Y, Cheng G, Wu H. Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation. Mol Cell. 2010 Apr 9;38(1):101-13. PMID:20385093 doi:10.1016/j.molcel.2010.03.009
  15. ↑ Park YC, Burkitt V, Villa AR, Tong L, Wu H. Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999 Apr 8;398(6727):533-8. PMID:10206649 doi:http://dx.doi.org/10.1038/19110

1ca4, resolution 2.20Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1ca4&oldid=4004938"