| Structural highlights
Disease
[TNFL6_HUMAN] Autoimmune lymphoproliferative syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
[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.[1] The FasL intracellular domain (FasL ICD) cytoplasmic form induces gene transcription inhibition.[2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
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