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| | ==Structure of Lymphotoxin alpha bound to anti-LTa Fab== | | ==Structure of Lymphotoxin alpha bound to anti-LTa Fab== |
| - | <StructureSection load='4mxv' size='340' side='right' caption='[[4mxv]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4mxv' size='340' side='right'caption='[[4mxv]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mxv]] is a 9 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=4MXV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MXV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mxv]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MXV FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tnr|1tnr]], [[4mxw|4mxw]]</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=4mxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mxv OCA], [https://pdbe.org/4mxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mxv RCSB], [https://www.ebi.ac.uk/pdbsum/4mxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mxv ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LTA, TNFB, TNFSF1 ([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=4mxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mxv OCA], [http://pdbe.org/4mxv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mxv RCSB], [http://www.ebi.ac.uk/pdbsum/4mxv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mxv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TNFB_HUMAN TNFB_HUMAN]] Genetic variations in LTA are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[http://omim.org/entry/607507 607507]]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). | + | [https://www.uniprot.org/uniprot/TNFB_HUMAN TNFB_HUMAN] Genetic variations in LTA are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[https://omim.org/entry/607507 607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNFB_HUMAN TNFB_HUMAN]] Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and cytotoxic for a wide range of tumor cells in vitro and in vivo. | + | [https://www.uniprot.org/uniprot/TNFB_HUMAN TNFB_HUMAN] Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and cytotoxic for a wide range of tumor cells in vitro and in vivo. |
| | <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== |
| - | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hymowitz, S G]] | + | [[Category: Large Structures]] |
| - | [[Category: Yin, J P]] | + | [[Category: Hymowitz SG]] |
| - | [[Category: Auto-immunity]] | + | [[Category: Yin JP]] |
| - | [[Category: Cytokine-immune system complex]]
| + | |
| - | [[Category: Lymphoid development]]
| + | |
| - | [[Category: Lymphotoxin alpha]]
| + | |
| - | [[Category: Lymphotoxin beta receptor]]
| + | |
| - | [[Category: Tnf]]
| + | |
| - | [[Category: Tnfr receptor]]
| + | |
| - | [[Category: Tumor immunity]]
| + | |
| - | [[Category: Tumor necrosis factor]]
| + | |
| Structural highlights
Disease
TNFB_HUMAN Genetic variations in LTA are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
Function
TNFB_HUMAN Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and cytotoxic for a wide range of tumor cells in vitro and in vivo.
Publication Abstract from PubMed
Homotrimeric TNF superfamily ligands signal by inducing trimers of their cognate receptors. As a biologically active heterotrimer, Lymphotoxin(LT)alpha1beta2 is unique in the TNF superfamily. How the three unique potential receptor-binding interfaces in LTalpha1beta2 trigger signaling via LTbeta Receptor (LTbetaR) resulting in lymphoid organogenesis and propagation of inflammatory signals is poorly understood. Here we show that LTalpha1beta2 possesses two binding sites for LTbetaR with distinct affinities and that dimerization of LTbetaR by LTalpha1beta2 is necessary and sufficient for signal transduction. The crystal structure of a complex formed by LTalpha1beta2, LTbetaR, and the fab fragment of an antibody that blocks LTbetaR activation reveals the lower affinity receptor-binding site. Mutations targeting each potential receptor-binding site in an engineered single-chain variant of LTalpha1beta2 reveal the high-affinity site. NF-kappaB reporter assays further validate that disruption of receptor interactions at either site is sufficient to prevent signaling via LTbetaR.
Dimerization of LTbetaR by LTalpha1beta2 is necessary and sufficient for signal transduction.,Sudhamsu J, Yin J, Chiang EY, Starovasnik MA, Grogan JL, Hymowitz SG Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19896-901. doi:, 10.1073/pnas.1310838110. Epub 2013 Nov 18. PMID:24248355[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sudhamsu J, Yin J, Chiang EY, Starovasnik MA, Grogan JL, Hymowitz SG. Dimerization of LTbetaR by LTalpha1beta2 is necessary and sufficient for signal transduction. Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19896-901. doi:, 10.1073/pnas.1310838110. Epub 2013 Nov 18. PMID:24248355 doi:http://dx.doi.org/10.1073/pnas.1310838110
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