1qqd
From Proteopedia
(Difference between revisions)
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<StructureSection load='1qqd' size='340' side='right'caption='[[1qqd]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='1qqd' size='340' side='right'caption='[[1qqd]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1qqd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[1qqd]] 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=1QQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QQD FirstGlance]. <br> |
| - | </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=1qqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qqd OCA], [https://pdbe.org/1qqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qqd RCSB], [https://www.ebi.ac.uk/pdbsum/1qqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qqd 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]] 2.7Å</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=1qqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qqd OCA], [https://pdbe.org/1qqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qqd RCSB], [https://www.ebi.ac.uk/pdbsum/1qqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qqd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | + | [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> | |
== Function == | == Function == | ||
| - | + | [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> | |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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=1qqd 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=1qqd ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). Relative to HLA-A2, the peptide binding groove is widened around the COOH terminus of the alpha 1 helix, which contains residues that determine the specificity of HLA-Cw4 for the inhibitory NK receptor, KIR2D. The structure reveals an unusual pattern of internal hydrogen bonding among peptide residues. The peptide is anchored in four specificity pockets in the cleft and secured by extensive hydrogen bonds between the peptide main chain and the cleft. The surface of HLA-Cw4 has electrostatic complementarity to the surface of the NK cell inhibitory receptor KIR2D. | ||
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| - | Structure of human histocompatibility leukocyte antigen (HLA)-Cw4, a ligand for the KIR2D natural killer cell inhibitory receptor.,Fan QR, Wiley DC J Exp Med. 1999 Jul 5;190(1):113-23. PMID:10429675<ref>PMID:10429675</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1qqd" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | ||
*[[MHC 3D structures|MHC 3D structures]] | *[[MHC 3D structures|MHC 3D structures]] | ||
| + | *[[MHC I 3D structures|MHC I 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Fan | + | [[Category: Fan QR]] |
| - | [[Category: Wiley | + | [[Category: Wiley DC]] |
| - | + | ||
| - | + | ||
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Revision as of 06:06, 17 April 2024
CRYSTAL STRUCTURE OF HLA-CW4, A LIGAND FOR THE KIR2D NATURAL KILLER CELL INHIBITORY RECEPTOR
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