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| | ==Crystal structure of the human leukocyte-associated Ig-like receptor-1 (LAIR-1)== | | ==Crystal structure of the human leukocyte-associated Ig-like receptor-1 (LAIR-1)== |
| - | <StructureSection load='3kgr' size='340' side='right' caption='[[3kgr]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3kgr' size='340' side='right'caption='[[3kgr]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kgr]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KGR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kgr]] is a 3 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=3KGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KGR FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LAIR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kgr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kgr RCSB], [http://www.ebi.ac.uk/pdbsum/3kgr PDBsum]</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=3kgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kgr OCA], [https://pdbe.org/3kgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kgr RCSB], [https://www.ebi.ac.uk/pdbsum/3kgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kgr ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LAIR1_HUMAN LAIR1_HUMAN] Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells.<ref>PMID:9285412</ref> <ref>PMID:10229813</ref> <ref>PMID:10764762</ref> <ref>PMID:9692876</ref> <ref>PMID:11069054</ref> <ref>PMID:11160222</ref> <ref>PMID:12072189</ref> <ref>PMID:15939744</ref> <ref>PMID:15950745</ref> <ref>PMID:16380958</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kg/3kgr_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kg/3kgr_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kgr ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.,Brondijk TH, de Ruiter T, Ballering J, Wienk H, Lebbink RJ, van Ingen H, Boelens R, Farndale RW, Meyaard L, Huizinga EG Blood. 2010 Feb 18;115(7):1364-73. Epub 2009 Dec 10. PMID:20007810<ref>PMID:20007810</ref> | | Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.,Brondijk TH, de Ruiter T, Ballering J, Wienk H, Lebbink RJ, van Ingen H, Boelens R, Farndale RW, Meyaard L, Huizinga EG Blood. 2010 Feb 18;115(7):1364-73. Epub 2009 Dec 10. PMID:20007810<ref>PMID:20007810</ref> |
| | | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3kgr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Leukocyte-associated immunoglobulin-like receptor|Leukocyte-associated immunoglobulin-like receptor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ballering, J.]] | + | [[Category: Large Structures]] |
| - | [[Category: Brondijk, T H.C.]] | + | [[Category: Ballering J]] |
| - | [[Category: Huizinga, E G.]] | + | [[Category: Brondijk THC]] |
| - | [[Category: Cell membrane]] | + | [[Category: Huizinga EG]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Ig-like domain]]
| + | |
| - | [[Category: Immune response]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin domain]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Receptor]]
| + | |
| Structural highlights
Function
LAIR1_HUMAN Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), one of the most widely spread immune receptors, attenuates immune cell activation when bound to specific sites in collagen. The collagen-binding domain of LAIR-1 is homologous to that of glycoprotein VI (GPVI), a collagen receptor crucial for platelet activation. Because LAIR-1 and GPVI also display overlapping collagen-binding specificities, a common structural basis for collagen recognition would appear likely. Therefore, it is crucial to gain insight into the molecular interaction of both receptors with their ligand to prevent unwanted cross-reactions during therapeutic intervention. We determined the crystal structure of LAIR-1 and mapped its collagen-binding site by nuclear magnetic resonance (NMR) titrations and mutagenesis. Our data identify R59, E61, and W109 as key residues for collagen interaction. These residues are strictly conserved in LAIR-1 and GPVI alike; however, they are located outside the previously proposed GPVI collagen-binding site. Our data provide evidence for an unanticipated mechanism of collagen recognition common to LAIR-1 and GPVI. This fundamental insight will contribute to the exploration of specific means of intervention in collagen-induced signaling in immunity and hemostasis.
Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.,Brondijk TH, de Ruiter T, Ballering J, Wienk H, Lebbink RJ, van Ingen H, Boelens R, Farndale RW, Meyaard L, Huizinga EG Blood. 2010 Feb 18;115(7):1364-73. Epub 2009 Dec 10. PMID:20007810[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Meyaard L, Adema GJ, Chang C, Woollatt E, Sutherland GR, Lanier LL, Phillips JH. LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Immunity. 1997 Aug;7(2):283-90. PMID:9285412
- ↑ Meyaard L, Hurenkamp J, Clevers H, Lanier LL, Phillips JH. Leukocyte-associated Ig-like receptor-1 functions as an inhibitory receptor on cytotoxic T cells. J Immunol. 1999 May 15;162(10):5800-4. PMID:10229813
- ↑ Xu M, Zhao R, Zhao ZJ. Identification and characterization of leukocyte-associated Ig-like receptor-1 as a major anchor protein of tyrosine phosphatase SHP-1 in hematopoietic cells. J Biol Chem. 2000 Jun 9;275(23):17440-6. PMID:10764762 doi:10.1074/jbc.M001313200
- ↑ Poggi A, Tomasello E, Ferrero E, Zocchi MR, Moretta L. p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor. Eur J Immunol. 1998 Jul;28(7):2086-91. PMID:9692876 doi:10.1002/(SICI)1521-4141(199807)28:07<2086::AID-IMMU2086>3.0.CO;2-T
- ↑ Poggi A, Pellegatta F, Leone BE, Moretta L, Zocchi MR. Engagement of the leukocyte-associated Ig-like receptor-1 induces programmed cell death and prevents NF-kappaB nuclear translocation in human myeloid leukemias. Eur J Immunol. 2000 Oct;30(10):2751-8. PMID:11069054
- ↑ Sathish JG, Johnson KG, Fuller KJ, LeRoy FG, Meyaard L, Sims MJ, Matthews RJ. Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells. J Immunol. 2001 Feb 1;166(3):1763-70. PMID:11160222
- ↑ Saverino D, Fabbi M, Merlo A, Ravera G, Grossi CE, Ciccone E. Surface density expression of the leukocyte-associated Ig-like receptor-1 is directly related to inhibition of human T-cell functions. Hum Immunol. 2002 Jul;63(7):534-46. PMID:12072189
- ↑ Merlo A, Tenca C, Fais F, Battini L, Ciccone E, Grossi CE, Saverino D. Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and cytokine production by human B lymphocytes. Clin Diagn Lab Immunol. 2005 Jun;12(6):705-12. PMID:15939744 doi:12/6/705
- ↑ Maasho K, Masilamani M, Valas R, Basu S, Coligan JE, Borrego F. The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at high levels by human naive T cells and inhibits TCR mediated activation. Mol Immunol. 2005 Aug;42(12):1521-30. Epub 2005 Feb 24. PMID:15950745 doi:10.1016/j.molimm.2005.01.004
- ↑ Verbrugge A, Rijkers ES, de Ruiter T, Meyaard L. Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase. Eur J Immunol. 2006 Jan;36(1):190-8. PMID:16380958 doi:10.1002/eji.200535226
- ↑ Brondijk TH, de Ruiter T, Ballering J, Wienk H, Lebbink RJ, van Ingen H, Boelens R, Farndale RW, Meyaard L, Huizinga EG. Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI. Blood. 2010 Feb 18;115(7):1364-73. Epub 2009 Dec 10. PMID:20007810 doi:10.1182/blood-2009-10-246322
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