6ng3

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human CD160 and HVEM complex

Structural highlights

6ng3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.88Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BY55_HUMAN CD160 antigen: Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells (PubMed:19109136, PubMed:11978774, PubMed:17307798). Receptor for both classical and non-classical MHC class I molecules (PubMed:9973372, PubMed:12486241). In the context of acute viral infection, recognizes HLA-C and triggers NK cell cytotoxic activity, likely playing a role in anti-viral innate immune response (PubMed:12486241). On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells (PubMed:9973372). Upon persistent antigen stimulation, such as occurs during chronic viral infection, may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion (PubMed:25255144). On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites (PubMed:16809620). Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response (By similarity). On activated CD4+ T cells, interacts with TNFRSF14 and downregulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050). In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and proinflammatory cytokines (By similarity).[UniProtKB:O88875]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] CD160 antigen, soluble form: The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions.^[9] TNR14_HUMAN Receptor for BTLA. Receptor for TNFSF14/LIGHT and homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte activation. Plays an important role in HSV pathogenesis because it enhanced the entry of several wild-type HSV strains of both serotypes into CHO cells, and mediated HSV entry into activated human T-cells.^[10]

Publication Abstract from PubMed

CD160 is a signaling molecule that interacts with herpes virus entry mediator (HVEM) and contributes to a wide range of immune responses, including T cell inhibition, natural killer cell activation, and mucosal immunity. GPI-anchored and transmembrane isoforms of CD160 share the same ectodomain responsible for HVEM engagement, which leads to bidirectional signaling. Despite the importance of the CD160:HVEM signaling axis and its therapeutic relevance, the structural and mechanistic basis underlying CD160-HVEM engagement has not been described. We report the crystal structures of the human CD160 extracellular domain and its complex with human HVEM. CD160 adopts a unique variation of the immunoglobulin fold and exists as a monomer in solution. The CD160:HVEM assembly exhibits a 1:1 stoichiometry and a binding interface similar to that observed in the BTLA:HVEM complex. Our work reveals the chemical and physical determinants underlying CD160:HVEM recognition and initiation of associated signaling processes.

Structural Basis of CD160:HVEM Recognition.,Liu W, Garrett SC, Fedorov EV, Ramagopal UA, Garforth SJ, Bonanno JB, Almo SC Structure. 2019 Jun 19. pii: S0969-2126(19)30172-8. doi:, 10.1016/j.str.2019.05.010. PMID:31230945^[11]

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

References

↑ Nikolova M, Marie-Cardine A, Boumsell L, Bensussan A. BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression. Int Immunol. 2002 May;14(5):445-51. doi: 10.1093/intimm/14.5.445. PMID:11978774 doi:http://dx.doi.org/10.1093/intimm/14.5.445
↑ Le Bouteiller P, Barakonyi A, Giustiniani J, Lenfant F, Marie-Cardine A, Aguerre-Girr M, Rabot M, Hilgert I, Mami-Chouaib F, Tabiasco J, Boumsell L, Bensussan A. Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16963-8. doi:, 10.1073/pnas.012681099. Epub 2002 Dec 16. PMID:12486241 doi:http://dx.doi.org/10.1073/pnas.012681099
↑ Fons P, Chabot S, Cartwright JE, Lenfant F, L'Faqihi F, Giustiniani J, Herault JP, Gueguen G, Bono F, Savi P, Aguerre-Girr M, Fournel S, Malecaze F, Bensussan A, Plouet J, Le Bouteiller P. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells. Blood. 2006 Oct 15;108(8):2608-15. doi: 10.1182/blood-2005-12-019919. Epub 2006, Jun 29. PMID:16809620 doi:http://dx.doi.org/10.1182/blood-2005-12-019919
↑ Rabot M, El Costa H, Polgar B, Marie-Cardine A, Aguerre-Girr M, Barakonyi A, Valitutti S, Bensussan A, Le Bouteiller P. CD160-activating NK cell effector functions depend on the phosphatidylinositol 3-kinase recruitment. Int Immunol. 2007 Apr;19(4):401-9. doi: 10.1093/intimm/dxm005. Epub 2007 Feb 16. PMID:17307798 doi:http://dx.doi.org/10.1093/intimm/dxm005
↑ Cai G, Anumanthan A, Brown JA, Greenfield EA, Zhu B, Freeman GJ. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol. 2008 Feb;9(2):176-85. doi: 10.1038/ni1554. Epub 2008 Jan 13. PMID:18193050 doi:http://dx.doi.org/10.1038/ni1554
↑ Giustiniani J, Bensussan A, Marie-Cardine A. Identification and characterization of a transmembrane isoform of CD160 (CD160-TM), a unique activating receptor selectively expressed upon human NK cell activation. J Immunol. 2009 Jan 1;182(1):63-71. doi: 10.4049/jimmunol.182.1.63. PMID:19109136 doi:http://dx.doi.org/10.4049/jimmunol.182.1.63
↑ Vigano S, Banga R, Bellanger F, Pellaton C, Farina A, Comte D, Harari A, Perreau M. CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. PLoS Pathog. 2014 Sep 25;10(9):e1004380. doi: 10.1371/journal.ppat.1004380., eCollection 2014 Sep. PMID:25255144 doi:http://dx.doi.org/10.1371/journal.ppat.1004380
↑ Agrawal S, Marquet J, Freeman GJ, Tawab A, Bouteiller PL, Roth P, Bolton W, Ogg G, Boumsell L, Bensussan A. Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. J Immunol. 1999 Feb 1;162(3):1223-6. PMID:9973372
↑ Giustiniani J, Marie-Cardine A, Bensussan A. A soluble form of the MHC class I-specific CD160 receptor is released from human activated NK lymphocytes and inhibits cell-mediated cytotoxicity. J Immunol. 2007 Feb 1;178(3):1293-300. doi: 10.4049/jimmunol.178.3.1293. PMID:17237375 doi:http://dx.doi.org/10.4049/jimmunol.178.3.1293
↑ Montgomery RI, Warner MS, Lum BJ, Spear PG. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell. 1996 Nov 1;87(3):427-36. PMID:8898196
↑ Liu W, Garrett SC, Fedorov EV, Ramagopal UA, Garforth SJ, Bonanno JB, Almo SC. Structural Basis of CD160:HVEM Recognition. Structure. 2019 Jun 19. pii: S0969-2126(19)30172-8. doi:, 10.1016/j.str.2019.05.010. PMID:31230945 doi:http://dx.doi.org/10.1016/j.str.2019.05.010

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ng3"

Categories: Homo sapiens | Large Structures | Almo SC | Bonanno J | Liu W

@@ Line 3: / Line 3: @@
 <StructureSection load='6ng3' size='340' side='right'caption='[[6ng3]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ng3]] is a 1 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=6NG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NG3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ng3]] is a 1 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=6NG3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NG3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 2.88&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF14, HVEA, HVEM, UNQ329/PRO509 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=MG:MAGNESIUM+ION'>MG</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ng3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ng3 OCA], [http://pdbe.org/6ng3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ng3 RCSB], [http://www.ebi.ac.uk/pdbsum/6ng3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ng3 ProSAT]</span></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=6ng3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ng3 OCA], [https://pdbe.org/6ng3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ng3 RCSB], [https://www.ebi.ac.uk/pdbsum/6ng3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ng3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/BY55_HUMAN BY55_HUMAN]] CD160 antigen: Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells (PubMed:19109136, PubMed:11978774, PubMed:17307798). Receptor for both classical and non-classical MHC class I molecules (PubMed:9973372, PubMed:12486241). In the context of acute viral infection, recognizes HLA-C and triggers NK cell cytotoxic activity, likely playing a role in anti-viral innate immune response (PubMed:12486241). On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells (PubMed:9973372). Upon persistent antigen stimulation, such as occurs during chronic viral infection, may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion (PubMed:25255144). On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites (PubMed:16809620). Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response (By similarity). On activated CD4+ T cells, interacts with TNFRSF14 and downregulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050). In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and proinflammatory cytokines (By similarity).[UniProtKB:O88875]<ref>PMID:11978774</ref> <ref>PMID:12486241</ref> <ref>PMID:16809620</ref> <ref>PMID:17307798</ref> <ref>PMID:18193050</ref> <ref>PMID:19109136</ref> <ref>PMID:25255144</ref> <ref>PMID:9973372</ref>   CD160 antigen, soluble form: The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions.<ref>PMID:17237375</ref>
+[https://www.uniprot.org/uniprot/BY55_HUMAN BY55_HUMAN] CD160 antigen: Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells (PubMed:19109136, PubMed:11978774, PubMed:17307798). Receptor for both classical and non-classical MHC class I molecules (PubMed:9973372, PubMed:12486241). In the context of acute viral infection, recognizes HLA-C and triggers NK cell cytotoxic activity, likely playing a role in anti-viral innate immune response (PubMed:12486241). On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells (PubMed:9973372). Upon persistent antigen stimulation, such as occurs during chronic viral infection, may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion (PubMed:25255144). On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites (PubMed:16809620). Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response (By similarity). On activated CD4+ T cells, interacts with TNFRSF14 and downregulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050). In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and proinflammatory cytokines (By similarity).[UniProtKB:O88875]<ref>PMID:11978774</ref> <ref>PMID:12486241</ref> <ref>PMID:16809620</ref> <ref>PMID:17307798</ref> <ref>PMID:18193050</ref> <ref>PMID:19109136</ref> <ref>PMID:25255144</ref> <ref>PMID:9973372</ref>   CD160 antigen, soluble form: The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions.<ref>PMID:17237375</ref> [https://www.uniprot.org/uniprot/TNR14_HUMAN TNR14_HUMAN] Receptor for BTLA. Receptor for TNFSF14/LIGHT and homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte activation. Plays an important role in HSV pathogenesis because it enhanced the entry of several wild-type HSV strains of both serotypes into CHO cells, and mediated HSV entry into activated human T-cells.<ref>PMID:8898196</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Almo, S C]]
+[[Category: Almo SC]]
-[[Category: Bonanno, J]]
+[[Category: Bonanno J]]
-[[Category: Liu, W]]
+[[Category: Liu W]]
-[[Category: Btla]]
-[[Category: Cd160]]
-[[Category: Gd]]
-[[Category: Hvem]]
-[[Category: Immune system]]

6ng3

From Proteopedia

Current revision

Crystal structure of human CD160 and HVEM complex

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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