2gkw

From Proteopedia

(Difference between revisions)

Revision as of 08:07, 16 January 2015

Key contacts promote recongnito of BAFF-R by TRAF3

Structural highlights

2gkw is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	TRAF3, CAP1, CRAF1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[TRAF3_HUMAN] Defects in TRAF3 are the cause of susceptibility to herpes simplex encephalitis 3 (HSE3) [MIM:614849]. A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.^[1]

Function

[TRAF3_HUMAN] Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

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

B cell-activating factor belonging to the TNF family receptor (BAFF-R), a member of the TNFR superfamily, plays a role in autoimmunity after ligation with BAFF ligand (also called TALL-1, BLyS, THANK, or zTNF4). BAFF/BAFF-R interactions are critical for B cell regulation, and signaling from this ligand-receptor complex results in NF-kappaB activation. Most TNFRs transmit signals intracellularly by recruitment of adaptor proteins called TNFR-associated factors (TRAFs). However, BAFF-R binds only one TRAF adaptor, TRAF3, and this interaction negatively regulates activation of NF-kappaB. In this study, we report the crystal structure of a 24-residue fragment of the cytoplasmic portion of BAFF-R bound in complex with TRAF3. The recognition motif (162)PVPAT(166) in BAFF-R is accommodated in the same binding crevice on TRAF3 that binds two related TNFRs, CD40 and LTbetaR, but is presented in a completely different structural framework. This region of BAFF-R assumes an open conformation with two extended strands opposed at right angles that each make contacts with TRAF3. The recognition motif is located in the N-terminal arm and intermolecular contacts mediate TRAF recognition. In the C-terminal arm, key stabilizing contacts are made, including critical hydrogen bonds with Gln(379) in TRAF3 that define the molecular basis for selective binding of BAFF-R solely to this member of the TRAF family. A dynamic conformational adjustment of Tyr(377) in TRAF3 occurs forming a new intermolecular contact with BAFF-R that stabilizes the complex. The structure of the complex provides a molecular explanation for binding affinities and selective protein interactions in TNFR-TRAF interactions.

Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulation.,Ni CZ, Oganesyan G, Welsh K, Zhu X, Reed JC, Satterthwait AC, Cheng G, Ely KR J Immunol. 2004 Dec 15;173(12):7394-400. PMID:15585864^[8]

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

References

↑ Perez de Diego R, Sancho-Shimizu V, Lorenzo L, Puel A, Plancoulaine S, Picard C, Herman M, Cardon A, Durandy A, Bustamante J, Vallabhapurapu S, Bravo J, Warnatz K, Chaix Y, Cascarrigny F, Lebon P, Rozenberg F, Karin M, Tardieu M, Al-Muhsen S, Jouanguy E, Zhang SY, Abel L, Casanova JL. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity. 2010 Sep 24;33(3):400-11. doi: 10.1016/j.immuni.2010.08.014. Epub 2010 , Sep 9. PMID:20832341 doi:10.1016/j.immuni.2010.08.014
↑ 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
↑ Liao G, Zhang M, Harhaj EW, Sun SC. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem. 2004 Jun 18;279(25):26243-50. Epub 2004 Apr 14. PMID:15084608 doi:10.1074/jbc.M403286200
↑ Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O'Rourke KM, Eby M, Pietras E, Cheng G, Bazan JF, Zhang Z, Arnott D, Dixit VM. DUBA: a deubiquitinase that regulates type I interferon production. Science. 2007 Dec 7;318(5856):1628-32. Epub 2007 Nov 8. PMID:17991829 doi:10.1126/science.1145918
↑ Mao AP, Li S, Zhong B, Li Y, Yan J, Li Q, Teng C, Shu HB. Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response. J Biol Chem. 2010 Mar 26;285(13):9470-6. doi: 10.1074/jbc.M109.071043. Epub 2010 , Jan 22. PMID:20097753 doi:10.1074/jbc.M109.071043
↑ Bista P, Zeng W, Ryan S, Bailly V, Browning JL, Lukashev ME. TRAF3 controls activation of the canonical and alternative NFkappaB by the lymphotoxin beta receptor. J Biol Chem. 2010 Apr 23;285(17):12971-8. doi: 10.1074/jbc.M109.076091. Epub 2010, Feb 25. PMID:20185819 doi:10.1074/jbc.M109.076091
↑ 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
↑ Ni CZ, Oganesyan G, Welsh K, Zhu X, Reed JC, Satterthwait AC, Cheng G, Ely KR. Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulation. J Immunol. 2004 Dec 15;173(12):7394-400. PMID:15585864

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gkw"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2gkw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GKW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GKW FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRAF3, CAP1, CRAF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRAF3, CAP1, CRAF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gkw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gkw RCSB], [http://www.ebi.ac.uk/pdbsum/2gkw 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=2gkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gkw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gkw RCSB], [http://www.ebi.ac.uk/pdbsum/2gkw PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/TRAF3_HUMAN TRAF3_HUMAN]] Defects in TRAF3 are the cause of susceptibility to herpes simplex encephalitis 3 (HSE3) [MIM:[http://omim.org/entry/614849 614849]]. A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.<ref>PMID:20832341</ref>
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ely, K R.]]
+[[Category: Ely, K R]]
 [[Category: Apoptosis]]
 [[Category: Baff receptor]]

2gkw

From Proteopedia

Revision as of 08:07, 16 January 2015

Key contacts promote recongnito of BAFF-R by TRAF3

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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