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| | <StructureSection load='4ht1' size='340' side='right'caption='[[4ht1]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='4ht1' size='340' side='right'caption='[[4ht1]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ht1]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HT1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ht1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HT1 FirstGlance]. <br> |
| - | </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=4ht1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ht1 OCA], [http://pdbe.org/4ht1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ht1 RCSB], [http://www.ebi.ac.uk/pdbsum/4ht1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ht1 ProSAT]</span></td></tr> | + | </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=4ht1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ht1 OCA], [https://pdbe.org/4ht1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ht1 RCSB], [https://www.ebi.ac.uk/pdbsum/4ht1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ht1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNF12_HUMAN TNF12_HUMAN]] Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines.<ref>PMID:10085077</ref> | + | [https://www.uniprot.org/uniprot/TNF12_HUMAN TNF12_HUMAN] Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines.<ref>PMID:10085077</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[Tumor necrosis factor ligand superfamily|Tumor necrosis factor ligand superfamily]] | + | *[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] |
| - | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | + | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Lammens, A]] | + | [[Category: Lammens A]] |
| - | [[Category: Antibody fab]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Extracellular thd domain]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Membrane bound]]
| + | |
| - | [[Category: Tnf homology domain]]
| + | |
| - | [[Category: Tweak receptor]]
| + | |
| Structural highlights
Function
TNF12_HUMAN Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines.[1]
Publication Abstract from PubMed
The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine playing a key role in tissue regeneration and remodeling. Dysregulation of TWEAK signaling is involved in various pathological processes like autoimmune diseases and cancer. The unique interaction with its cognate receptor Fn14 makes both ligand and receptor promising targets for novel therapeutics. To gain insights into this important signaling pathway, we determined the structure of soluble human TWEAK in complex with the Fab fragment of an antibody selected for inhibition of receptor binding. In the crystallized complex TWEAK is bound by three Fab fragments of the neutralizing antibody. Homology modeling shows that Fab binding overlaps with the putative Fn14 binding site of TWEAK. Docking of the Fn14 cysteine rich domain (CRD) to that site generates a highly complementary interface with perfectly opposing charged and hydrophobic residues. Taken together the presented structure provides new insights into the biology of TWEAK and the TWEAK/Fn14 pathway, which will help to optimize the therapeutic strategy for treatment of related cancer types and autoimmune diseases.
Crystal Structure of Human TWEAK in Complex with the Fab Fragment of a Neutralizing Antibody Reveals Insights into Receptor Binding.,Lammens A, Baehner M, Kohnert U, Niewoehner J, von Proff L, Schraeml M, Lammens K, Hopfner KP PLoS One. 2013 May 8;8(5):e62697. doi: 10.1371/journal.pone.0062697. Print 2013. PMID:23667509[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lynch CN, Wang YC, Lund JK, Chen YW, Leal JA, Wiley SR. TWEAK induces angiogenesis and proliferation of endothelial cells. J Biol Chem. 1999 Mar 26;274(13):8455-9. PMID:10085077
- ↑ Lammens A, Baehner M, Kohnert U, Niewoehner J, von Proff L, Schraeml M, Lammens K, Hopfner KP. Crystal Structure of Human TWEAK in Complex with the Fab Fragment of a Neutralizing Antibody Reveals Insights into Receptor Binding. PLoS One. 2013 May 8;8(5):e62697. doi: 10.1371/journal.pone.0062697. Print 2013. PMID:23667509 doi:10.1371/journal.pone.0062697
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