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| | ==Crystal structure of NKp65 bound to its ligand KACL== | | ==Crystal structure of NKp65 bound to its ligand KACL== |
| - | <StructureSection load='4iop' size='340' side='right' caption='[[4iop]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4iop' size='340' side='right'caption='[[4iop]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iop]] is a 2 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=4IOP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IOP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iop]] is a 2 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=4IOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IOP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 3.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLEC2A, KACL, UNQ5792/PRO19597 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), KLRF2 ([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=MAN:ALPHA-D-MANNOSE'>MAN</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=4iop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iop OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iop RCSB], [http://www.ebi.ac.uk/pdbsum/4iop 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=4iop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iop OCA], [https://pdbe.org/4iop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iop RCSB], [https://www.ebi.ac.uk/pdbsum/4iop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iop ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLC2A_HUMAN CLC2A_HUMAN]] Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity.<ref>PMID:18550855</ref> <ref>PMID:20194751</ref> [[http://www.uniprot.org/uniprot/KLRF2_HUMAN KLRF2_HUMAN]] C-type lectin-like receptor involved in natural killer cell mediated cytotoxicity and cytokine secretion in keratinocytes via its interaction with CLEC2A. | + | [https://www.uniprot.org/uniprot/CLC2A_HUMAN CLC2A_HUMAN] Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity.<ref>PMID:18550855</ref> <ref>PMID:20194751</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | 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 4iop" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Li, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Immune system]] | + | [[Category: Li Y]] |
| - | [[Category: Nk cell receptor]]
| + | |
| - | [[Category: Receptor-ligand complex]]
| + | |
| Structural highlights
Function
CLC2A_HUMAN Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity.[1] [2]
Publication Abstract from PubMed
The natural killer (NK) gene complex (NKC) encodes numerous C-type lectin-like receptors that govern the activity of NK cells. Although some of these receptors (Ly49s, NKG2D, CD94/NKG2A) recognize MHC or MHC-like molecules, others (Nkrp1, NKRP1A, NKp80, NKp65) instead bind C-type lectin-like ligands to which they are genetically linked in the NKC. To understand the basis for this recognition, we determined the structure of human NKp65, an activating receptor implicated in the immunosurveillance of skin, bound to its NKC-encoded ligand keratinocyte-associated C-type lectin (KACL). Whereas KACL forms a homodimer resembling other C-type lectin-like dimers, NKp65 is monomeric. The binding mode in the NKp65-KACL complex, in which a monomeric receptor engages a dimeric ligand, is completely distinct from those used by Ly49s, NKG2D, or CD94/NKG2A. The structure explains the exceptionally high affinity of the NKp65-KACL interaction compared with other cell-cell interaction pairs (KD = 6.7 x 10(-10) M), which may compensate for the monomeric nature of NKp65 to achieve cell activation. This previously unreported structure of an NKC-encoded receptor-ligand complex, coupled with mutational analysis of the interface, establishes a docking template that is directly applicable to other genetically linked pairs in the NKC, including Nkrp1-Clr, NKRP1A-LLT1, and NKp80-AICL.
Structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex.,Li Y, Wang Q, Chen S, Brown PH, Mariuzza RA Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11505-10. doi:, 10.1073/pnas.1303300110. Epub 2013 Jun 26. PMID:23803857[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huarte E, Cubillos-Ruiz JR, Nesbeth YC, Scarlett UK, Martinez DG, Engle XA, Rigby WF, Pioli PA, Guyre PM, Conejo-Garcia JR. PILAR is a novel modulator of human T-cell expansion. Blood. 2008 Aug 15;112(4):1259-68. doi: 10.1182/blood-2007-12-130773. Epub 2008, Jun 12. PMID:18550855 doi:10.1182/blood-2007-12-130773
- ↑ Spreu J, Kuttruff S, Stejfova V, Dennehy KM, Schittek B, Steinle A. Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5100-5. doi:, 10.1073/pnas.0913108107. Epub 2010 Mar 1. PMID:20194751 doi:10.1073/pnas.0913108107
- ↑ Li Y, Wang Q, Chen S, Brown PH, Mariuzza RA. Structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11505-10. doi:, 10.1073/pnas.1303300110. Epub 2013 Jun 26. PMID:23803857 doi:10.1073/pnas.1303300110
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