1im9

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[[Image:1im9.png|left|200px]]
 
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{{STRUCTURE_1im9| PDB=1im9 | SCENE= }}
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==Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1 bound to its MHC ligand HLA-Cw4==
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<StructureSection load='1im9' size='340' side='right'caption='[[1im9]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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===Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1 bound to its MHC ligand HLA-Cw4===
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1im9]] is a 7 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=1IM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IM9 FirstGlance]. <br>
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{{ABSTRACT_PUBMED_11323700}}
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1im9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1im9 OCA], [https://pdbe.org/1im9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1im9 RCSB], [https://www.ebi.ac.uk/pdbsum/1im9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1im9 ProSAT]</span></td></tr>
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==About this Structure==
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</table>
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[[1im9]] is a 7 chain structure of [[Beta-2 microglobulin]] and [[Major histocompatibility complex]] 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=1IM9 OCA].
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== Disease ==
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[https://www.uniprot.org/uniprot/HLAC_HUMAN HLAC_HUMAN] B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2). Disease susceptibility is associated with variants affecting the gene represented in this entry. Allele C*06:02 presents a melanocyte autoantigen ADAMTSL5 (VRSRRCLRL) to Valpha3S1/Vbeta13S1 TCR on CD8-positive T cells, and may trigger an autoimmune response against melanocytes.<ref>PMID:26621454</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/HLAC_HUMAN HLAC_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity (PubMed:20972337, PubMed:24091323, PubMed:20439706, PubMed:11172028, PubMed:20104487, PubMed:28649982, PubMed:29312307). In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells (PubMed:16141329). In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth (PubMed:20972337, PubMed:24091323). During viral infection, may present viral peptides with low affinity for KIRs, impeding KIR-mediated inhibition through peptide antagonism and favoring lysis of infected cells (PubMed:20439706). Presents a restricted repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-C-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection (PubMed:11172028, PubMed:20104487, PubMed:28649982). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (By similarity). Typically presents intracellular peptide antigens of 9 amino acids that arise from cytosolic proteolysis via proteasome. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Preferentially displays peptides having a restricted repertoire of hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val and Tyr) at the C-terminal anchor (PubMed:8265661, PubMed:25311805).[UniProtKB:P04439]<ref>PMID:11172028</ref> <ref>PMID:16141329</ref> <ref>PMID:20104487</ref> <ref>PMID:20439706</ref> <ref>PMID:20972337</ref> <ref>PMID:24091323</ref> <ref>PMID:25311805</ref> <ref>PMID:28649982</ref> <ref>PMID:29312307</ref> <ref>PMID:8265661</ref> ALLELE C*01:02: The peptide-bound form interacts with KIR2DL2 and KIR2DL3 inhibitory receptors on NK cells. The low affinity peptides compete with the high affinity peptides impeding KIR-mediated inhibition and favoring lysis of infected cells (PubMed:20439706). Presents to CD8-positive T cells a CMV epitope derived from UL83/pp65 (RCPEMISVL), an immediate-early antigen necessary for initiating viral replication (PubMed:12947002).<ref>PMID:12947002</ref> <ref>PMID:20439706</ref> ALLELE C*04:01: Presents a conserved HIV-1 epitope derived from env (SFNCGGEFF) to memory CD8-positive T cells, eliciting very strong IFNG responses (PubMed:20104487). Presents CMV epitope derived from UL83/pp65 (QYDPVAALF) to CD8-positive T cells, triggering T cell cytotoxic response (PubMed:12947002).<ref>PMID:12947002</ref> <ref>PMID:20104487</ref> ALLELE C*05:01: Presents HIV-1 epitope derived from rev (SAEPVPLQL) to CD8-positive T cells, triggering T cell cytotoxic response.<ref>PMID:11172028</ref> ALLELE C*06:02: In trophoblasts, interacts with KIR2DS2 on uterine NK cells and triggers NK cell activation, including secretion of cytokines such as GMCSF that enhances trophoblast migration.<ref>PMID:24091323</ref> ALLELE C*07:02: Plays an important role in the control of chronic CMV infection. Presents immunodominant CMV epitopes derived from IE1 (LSEFCRVL and CRVLCCYVL) and UL28 (FRCPRRFCF), both antigens synthesized during immediate-early period of viral replication. Elicits a strong anti-viral CD8-positive T cell immune response that increases markedly with age.<ref>PMID:29312307</ref> ALLELE C*08:01: Presents viral epitopes derived from CMV UL83 (VVCAHELVC) and IAV M1 (GILGFVFTL), triggering CD8-positive T cell cytotoxic response.<ref>PMID:12947002</ref> <ref>PMID:24990997</ref> ALLELE C*12:02: Presents CMV epitope derived from UL83 (VAFTSHEHF) to CD8-positive T cells.<ref>PMID:12947002</ref> ALLELE C*15:02: Presents CMV epitope derived from UL83 CC (VVCAHELVC) to CD8-positive T cells, triggering T cell cytotoxic response.<ref>PMID:12947002</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/1im9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1im9 ConSurf].
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<div style="clear:both"></div>
==See Also==
==See Also==
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*[[Beta-2 microglobulin|Beta-2 microglobulin]]
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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*[[Major histocompatibility complex|Major histocompatibility complex]]
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*[[MHC 3D structures|MHC 3D structures]]
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*[[MHC I 3D structures|MHC I 3D structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:011323700</ref><references group="xtra"/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Fan, Q R.]]
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[[Category: Large Structures]]
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[[Category: Long, E O.]]
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[[Category: Fan QR]]
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[[Category: Wiley, D C.]]
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[[Category: Long EO]]
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[[Category: Alpha helix]]
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[[Category: Wiley DC]]
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[[Category: Antiparallel beta sheet]]
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[[Category: Immune system]]
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[[Category: Immunoglobulin domain]]
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[[Category: Protein-protein complex]]
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Current revision

Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1 bound to its MHC ligand HLA-Cw4

PDB ID 1im9

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