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5l36

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Revision as of 12:23, 25 December 2019

Crystal Structure of a human FasL mutant in complex with human DcR3

Structural highlights

5l36 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5l19, 4msv
Gene:	TNFRSF6B, DCR3, TR6, UNQ186/PRO212 (HUMAN), FASLG, APT1LG1, CD95L, FASL, TNFSF6 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TNFL6_HUMAN] Autoimmune lymphoproliferative syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TNF6B_HUMAN] Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.^[1] [TNFL6_HUMAN] Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. May be involved in cytotoxic T-cell mediated apoptosis and in T-cell development. TNFRSF6/FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. Binding to the decoy receptor TNFRSF6B/DcR3 modulates its effects.^[2] The FasL intracellular domain (FasL ICD) cytoplasmic form induces gene transcription inhibition.^[3]

Publication Abstract from PubMed

The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3.

Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.,Liu W, Ramagopal U, Cheng H, Bonanno JB, Toro R, Bhosle R, Zhan C, Almo SC Structure. 2016 Nov 1;24(11):2016-2023. doi: 10.1016/j.str.2016.09.009. PMID:27806260^[4]

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

References

↑ Zhan C, Patskovsky Y, Yan Q, Li Z, Ramagopal U, Cheng H, Brenowitz M, Hui X, Nathenson SG, Almo SC. Decoy Strategies: The Structure of TL1A:DcR3 Complex. Structure. 2011 Feb 9;19(2):162-71. PMID:21300286 doi:10.1016/j.str.2010.12.004
↑ Kirkin V, Cahuzac N, Guardiola-Serrano F, Huault S, Luckerath K, Friedmann E, Novac N, Wels WS, Martoglio B, Hueber AO, Zornig M. The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. Cell Death Differ. 2007 Sep;14(9):1678-87. Epub 2007 Jun 8. PMID:17557115 doi:http://dx.doi.org/10.1038/sj.cdd.4402175
↑ Kirkin V, Cahuzac N, Guardiola-Serrano F, Huault S, Luckerath K, Friedmann E, Novac N, Wels WS, Martoglio B, Hueber AO, Zornig M. The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. Cell Death Differ. 2007 Sep;14(9):1678-87. Epub 2007 Jun 8. PMID:17557115 doi:http://dx.doi.org/10.1038/sj.cdd.4402175
↑ Liu W, Ramagopal U, Cheng H, Bonanno JB, Toro R, Bhosle R, Zhan C, Almo SC. Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. Structure. 2016 Nov 1;24(11):2016-2023. doi: 10.1016/j.str.2016.09.009. PMID:27806260 doi:http://dx.doi.org/10.1016/j.str.2016.09.009

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5l36"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of a human FasL mutant in complex with human DcR3==
-<StructureSection load='5l36' size='340' side='right' caption='[[5l36]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+<StructureSection load='5l36' size='340' side='right'caption='[[5l36]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l36]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L36 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l36]] is a 2 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=5L36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L36 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5l19|5l19]], [[4msv|4msv]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF6B, DCR3, TR6, UNQ186/PRO212 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FASLG, APT1LG1, CD95L, FASL, TNFSF6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5l36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l36 OCA], [http://pdbe.org/5l36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l36 RCSB], [http://www.ebi.ac.uk/pdbsum/5l36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l36 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 ==See Also==
+*[[Tumor necrosis factor ligand superfamily|Tumor necrosis factor ligand superfamily]]
 *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]]
 == References ==
@@ Line 28: / Line 30: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Almo, S C]]
 [[Category: Bonanno, J B]]

5l36

From Proteopedia

Revision as of 12:23, 25 December 2019

Crystal Structure of a human FasL mutant in complex with human DcR3

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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