1fll

From Proteopedia

(Difference between revisions)

Revision as of 11:11, 28 July 2021

MOLECULAR BASIS FOR CD40 SIGNALING MEDIATED BY TRAF3

Structural highlights

1fll is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1flk
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [TNR5_HUMAN] Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:606843]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.^[2]

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.^[3] ^[4] ^[5] ^[6] ^[7] ^[8] [TNR5_HUMAN] Receptor for TNFSF5/CD40LG.

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

Tumor necrosis factor receptors (TNFR) are single transmembrane-spanning glycoproteins that bind cytokines and trigger multiple signal transduction pathways. Many of these TNFRs rely on interactions with TRAF proteins that bind to the intracellular domain of the receptors. CD40 is a member of the TNFR family that binds to several different TRAF proteins. We have determined the crystal structure of a 20-residue fragment from the cytoplasmic domain of CD40 in complex with the TRAF domain of TRAF3. The CD40 fragment binds as a hairpin loop across the surface of the TRAF domain. Residues shown by mutagenesis and deletion analysis to be critical for TRAF3 binding are involved either in direct contact with TRAF3 or in intramolecular interactions that stabilize the hairpin. Comparison of the interactions of CD40 with TRAF3 vs. TRAF2 suggests that CD40 may assume different conformations when bound to different TRAF family members. This molecular adaptation may influence binding affinity and specific cellular triggers.

Molecular basis for CD40 signaling mediated by TRAF3.,Ni CZ, Welsh K, Leo E, Chiou CK, Wu H, Reed JC, Ely KR Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10395-9. PMID:10984535^[9]

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
↑ Ferrari S, Giliani S, Insalaco A, Al-Ghonaium A, Soresina AR, Loubser M, Avanzini MA, Marconi M, Badolato R, Ugazio AG, Levy Y, Catalan N, Durandy A, Tbakhi A, Notarangelo LD, Plebani A. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12614-9. PMID:11675497 doi:10.1073/pnas.221456898
↑ 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, Welsh K, Leo E, Chiou CK, Wu H, Reed JC, Ely KR. Molecular basis for CD40 signaling mediated by TRAF3. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10395-9. PMID:10984535

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fll"

@@ Line 3: / Line 3: @@
 <StructureSection load='1fll' size='340' side='right'caption='[[1fll]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fll]] is a 4 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=1FLL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FLL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fll]] is a 4 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=1FLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FLL FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1flk|1flk]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1flk|1flk]]</div></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=1fll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fll OCA], [http://pdbe.org/1fll PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fll RCSB], [http://www.ebi.ac.uk/pdbsum/1fll PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fll ProSAT]</span></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=1fll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fll OCA], [https://pdbe.org/1fll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fll RCSB], [https://www.ebi.ac.uk/pdbsum/1fll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fll ProSAT]</span></td></tr>
 </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>  [[http://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:[http://omim.org/entry/606843 606843]]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:11675497</ref>
+[[https://www.uniprot.org/uniprot/TRAF3_HUMAN TRAF3_HUMAN]] Defects in TRAF3 are the cause of susceptibility to herpes simplex encephalitis 3 (HSE3) [MIM:[https://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>  [[https://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:[https://omim.org/entry/606843 606843]]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.<ref>PMID:11675497</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/TRAF3_HUMAN 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.<ref>PMID:15383523</ref> <ref>PMID:15084608</ref> <ref>PMID:17991829</ref> <ref>PMID:20097753</ref> <ref>PMID:20185819</ref> <ref>PMID:19937093</ref>  [[http://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Receptor for TNFSF5/CD40LG.
+[[https://www.uniprot.org/uniprot/TRAF3_HUMAN 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.<ref>PMID:15383523</ref> <ref>PMID:15084608</ref> <ref>PMID:17991829</ref> <ref>PMID:20097753</ref> <ref>PMID:20185819</ref> <ref>PMID:19937093</ref>  [[https://www.uniprot.org/uniprot/TNR5_HUMAN TNR5_HUMAN]] Receptor for TNFSF5/CD40LG.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 30: @@
 </div>
 <div class="pdbe-citations 1fll" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]]
 == References ==
 <references/>

1fll

From Proteopedia

Revision as of 11:11, 28 July 2021

MOLECULAR BASIS FOR CD40 SIGNALING MEDIATED BY TRAF3

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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