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==== | ==The crystal structure of LIGHT in complex with HVEM and CD160== | ||
<StructureSection load='7msg' size='340' side='right'caption='[[7msg]]' scene=''> | <StructureSection load='7msg' size='340' side='right'caption='[[7msg]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7msg]] is a 6 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=7MSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MSG FirstGlance]. <br> | ||
</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=7msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7msg OCA], [https://pdbe.org/7msg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7msg RCSB], [https://www.ebi.ac.uk/pdbsum/7msg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7msg ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7msg OCA], [https://pdbe.org/7msg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7msg RCSB], [https://www.ebi.ac.uk/pdbsum/7msg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7msg ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/TNF14_HUMAN TNF14_HUMAN] Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HVEM is a TNF (tumor necrosis factor) receptor contributing to a broad range of immune functions involving diverse cell types. It interacts with a TNF ligand, LIGHT, and immunoglobulin (Ig) superfamily members BTLA and CD160. Assessing the functional impact of HVEM binding to specific ligands in different settings has been complicated by the multiple interactions of HVEM and HVEM binding partners. To dissect the molecular basis for multiple functions, we determined crystal structures that reveal the distinct HVEM surfaces that engage LIGHT or BTLA/CD160, including the human HVEM-LIGHT-CD160 ternary complex, with HVEM interacting simultaneously with both binding partners. Based on these structures, we generated mouse HVEM mutants that selectively recognized either the TNF or Ig ligands in vitro. Knockin mice expressing these muteins maintain expression of all the proteins in the HVEM network, yet they demonstrate selective functions for LIGHT in the clearance of bacteria in the intestine and for the Ig ligands in the amelioration of liver inflammation. | |||
HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.,Liu W, Chou TF, Garrett-Thomson SC, Seo GY, Fedorov E, Ramagopal UA, Bonanno JB, Wang Q, Kim K, Garforth SJ, Kakugawa K, Cheroutre H, Kronenberg M, Almo SC J Exp Med. 2021 Dec 6;218(12). pii: 212735. doi: 10.1084/jem.20211112. Epub 2021 , Oct 28. PMID:34709351<ref>PMID:34709351</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7msg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Tumor necrosis factor ligand superfamily 3D structures|Tumor necrosis factor ligand superfamily 3D structures]] | |||
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Almo SC]] | ||
[[Category: Bonanno JB]] | |||
[[Category: Fedorov E]] | |||
[[Category: Garrett-Thompson SC]] | |||
[[Category: Liu W]] | |||
[[Category: Ramagopal U]] | |||
Latest revision as of 14:35, 30 October 2024
The crystal structure of LIGHT in complex with HVEM and CD160The crystal structure of LIGHT in complex with HVEM and CD160
Structural highlights
FunctionTNF14_HUMAN Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus. Publication Abstract from PubMedHVEM is a TNF (tumor necrosis factor) receptor contributing to a broad range of immune functions involving diverse cell types. It interacts with a TNF ligand, LIGHT, and immunoglobulin (Ig) superfamily members BTLA and CD160. Assessing the functional impact of HVEM binding to specific ligands in different settings has been complicated by the multiple interactions of HVEM and HVEM binding partners. To dissect the molecular basis for multiple functions, we determined crystal structures that reveal the distinct HVEM surfaces that engage LIGHT or BTLA/CD160, including the human HVEM-LIGHT-CD160 ternary complex, with HVEM interacting simultaneously with both binding partners. Based on these structures, we generated mouse HVEM mutants that selectively recognized either the TNF or Ig ligands in vitro. Knockin mice expressing these muteins maintain expression of all the proteins in the HVEM network, yet they demonstrate selective functions for LIGHT in the clearance of bacteria in the intestine and for the Ig ligands in the amelioration of liver inflammation. HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160.,Liu W, Chou TF, Garrett-Thomson SC, Seo GY, Fedorov E, Ramagopal UA, Bonanno JB, Wang Q, Kim K, Garforth SJ, Kakugawa K, Cheroutre H, Kronenberg M, Almo SC J Exp Med. 2021 Dec 6;218(12). pii: 212735. doi: 10.1084/jem.20211112. Epub 2021 , Oct 28. PMID:34709351[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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