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| | ==Crystal structure of NKG2D in complex with ULBP6== | | ==Crystal structure of NKG2D in complex with ULBP6== |
| - | <StructureSection load='4s0u' size='340' side='right' caption='[[4s0u]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='4s0u' size='340' side='right'caption='[[4s0u]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4s0u]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S0U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S0U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4s0u]] 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=4S0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0U FirstGlance]. <br> |
| - | </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=4s0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0u OCA], [http://pdbe.org/4s0u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s0u RCSB], [http://www.ebi.ac.uk/pdbsum/4s0u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0u 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]] 2.35Å</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=4s0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0u OCA], [https://pdbe.org/4s0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0u RCSB], [https://www.ebi.ac.uk/pdbsum/4s0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NKG2D_HUMAN NKG2D_HUMAN]] Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes. | + | [https://www.uniprot.org/uniprot/NKG2D_HUMAN NKG2D_HUMAN] Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4s0u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4s0u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[NK cell receptor|NK cell receptor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mohammed, F]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Willcox, B E]] | + | [[Category: Large Structures]] |
| - | [[Category: Affinity and autoimmunity]] | + | [[Category: Mohammed F]] |
| - | [[Category: C-type lectin domain]] | + | [[Category: Willcox BE]] |
| - | [[Category: Graft versus leukaemia]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Leukaemia]]
| + | |
| - | [[Category: Nkg2d]]
| + | |
| - | [[Category: Nkg2dl]]
| + | |
| Structural highlights
Function
NKG2D_HUMAN Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes.
Publication Abstract from PubMed
NKG2D (natural killer group 2, member D) is an activating receptor found on the surface of immune cells, including natural killer (NK) cells, which regulates innate and adaptive immunity through recognition of the stress-induced ligands ULBP1 (UL16 binding protein 1) to ULBP6 and MICA/B. Similar to class I human leukocyte antigen (HLA), these NKG2D ligands have a major histocompatibility complex-like fold and exhibit pronounced polymorphism, which influences human disease susceptibility. However, whereas class I HLA polymorphisms occur predominantly in the alpha1alpha2 groove and affect antigen binding, the effects of most NKG2D ligand polymorphisms are unclear. We studied the molecular and functional consequences of the two major alleles of ULBP6, the most polymorphic ULBP gene, which are associated with autoimmunity and relapse after stem cell transplantation. Surface plasmon resonance and crystallography studies revealed that the arginine-to-leucine polymorphism within ULBP0602 affected the NKG2D-ULBP6 interaction by generating an energetic hotspot. This resulted in an NKG2D-ULBP0602 affinity of 15.5 nM, which is 10- to 1000-fold greater than the affinities of other ULBP-NKG2D interactions and limited NKG2D-mediated activation. In addition, soluble ULBP0602 exhibited high-affinity competitive binding for NKG2D and partially suppressed NKG2D-mediated activation of NK cells by other NKG2D ligands. These effects resulted in a decrease in a range of NKG2D-mediated effector functions. Our results reveal that ULBP polymorphisms affect the strength of human lymphocyte responses to cellular stress signals and may offer opportunities for therapeutic intervention.
A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D ligand binding.,Zuo J, Willcox CR, Mohammed F, Davey M, Hunter S, Khan K, Antoun A, Katakia P, Croudace J, Inman C, Parry H, Briggs D, Malladi R, Willcox BE, Moss P Sci Signal. 2017 May 30;10(481). pii: eaai8904. doi: 10.1126/scisignal.aai8904. PMID:28559451[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zuo J, Willcox CR, Mohammed F, Davey M, Hunter S, Khan K, Antoun A, Katakia P, Croudace J, Inman C, Parry H, Briggs D, Malladi R, Willcox BE, Moss P. A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D ligand binding. Sci Signal. 2017 May 30;10(481). pii: eaai8904. doi: 10.1126/scisignal.aai8904. PMID:28559451 doi:http://dx.doi.org/10.1126/scisignal.aai8904
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