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| | ==KIR3DL1 in complex with HLA-B*57:01.I80T== | | ==KIR3DL1 in complex with HLA-B*57:01.I80T== |
| - | <StructureSection load='3wuw' size='340' side='right' caption='[[3wuw]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3wuw' size='340' side='right'caption='[[3wuw]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wuw]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WUW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WUW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wuw]] is a 4 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=3WUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WUW FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2Å</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=3wuw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wuw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wuw RCSB], [http://www.ebi.ac.uk/pdbsum/3wuw PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wuw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wuw OCA], [https://pdbe.org/3wuw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wuw RCSB], [https://www.ebi.ac.uk/pdbsum/3wuw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wuw ProSAT]</span></td></tr> |
| | + | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | + | [https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KI3L1_HUMAN KI3L1_HUMAN]] Receptor on natural killer (NK) cells for HLA Bw4 allele. Inhibits the activity of NK cells thus preventing cell lysis. [[http://www.uniprot.org/uniprot/1B57_HUMAN 1B57_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity.,O'Connor GM, Vivian JP, Widjaja JM, Bridgeman JS, Gostick E, Lafont BA, Anderson SK, Price DA, Brooks AG, Rossjohn J, McVicar DW J Immunol. 2014 Mar 15;192(6):2875-84. doi: 10.4049/jimmunol.1303142. Epub 2014, Feb 21. PMID:24563253<ref>PMID:24563253</ref> | | Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity.,O'Connor GM, Vivian JP, Widjaja JM, Bridgeman JS, Gostick E, Lafont BA, Anderson SK, Price DA, Brooks AG, Rossjohn J, McVicar DW J Immunol. 2014 Mar 15;192(6):2875-84. doi: 10.4049/jimmunol.1303142. Epub 2014, Feb 21. PMID:24563253<ref>PMID:24563253</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 3wuw" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | + | *[[NK cell receptor|NK cell receptor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Rossjohn, J.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Vivian, J P.]] | + | [[Category: Large Structures]] |
| - | [[Category: Immune receptor complex]] | + | [[Category: Rossjohn J]] |
| - | [[Category: Protein binding]] | + | [[Category: Vivian JP]] |
| Structural highlights
Disease
IGKC_HUMAN Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:614102. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.[1]
Function
IGKC_HUMAN
Publication Abstract from PubMed
Killer Ig-like receptors (KIRs) control the activation of human NK cells via interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory receptor that recognizes a diverse array of HLA molecules expressing the Bw4 epitope, a group with multiple polymorphisms incorporating variants within the Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional significance in several disease states, including HIV infection. However, owing to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the mechanistic link with biological outcome remains unclear. In this study, we elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition. Mutational analysis revealed that KIR residues involved in water-mediated contacts with the HLA-presented peptide influence peptide binding specificity. In particular, residue 282 (glutamate) in the D2 domain underpins the lack of tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1 variants, defined by neighboring residue 283, displayed differential sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive selection during the evolution of human KIRs, also played a central role in Bw4 subtype recognition by KIR3DL1. Collectively, our findings uncover a common molecular regulator that controls HLA and peptide discrimination without participating directly in peptide-laden HLA interactions. Furthermore, they provide insight into the mechanics of interaction and generate simple, easily assessed criteria for the definition of KIR3DL1 functional groupings that will be relevant in many clinical applications, including bone marrow transplantation.
Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity.,O'Connor GM, Vivian JP, Widjaja JM, Bridgeman JS, Gostick E, Lafont BA, Anderson SK, Price DA, Brooks AG, Rossjohn J, McVicar DW J Immunol. 2014 Mar 15;192(6):2875-84. doi: 10.4049/jimmunol.1303142. Epub 2014, Feb 21. PMID:24563253[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stavnezer-Nordgren J, Kekish O, Zegers BJ. Molecular defects in a human immunoglobulin kappa chain deficiency. Science. 1985 Oct 25;230(4724):458-61. PMID:3931219
- ↑ O'Connor GM, Vivian JP, Widjaja JM, Bridgeman JS, Gostick E, Lafont BA, Anderson SK, Price DA, Brooks AG, Rossjohn J, McVicar DW. Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity. J Immunol. 2014 Mar 15;192(6):2875-84. doi: 10.4049/jimmunol.1303142. Epub 2014, Feb 21. PMID:24563253 doi:http://dx.doi.org/10.4049/jimmunol.1303142
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