4en3: Difference between revisions
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==Crystal structure of a human Valpha24(-) NKT TCR in complex with CD1d/alpha-galactosylceramide== | |||
<StructureSection load='4en3' size='340' side='right'caption='[[4en3]], [[Resolution|resolution]] 2.57Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4en3]] 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=4EN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EN3 FirstGlance]. <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]] 2.568Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGH:N-{(1S,2R,3S)-1-[(ALPHA-D-GALACTOPYRANOSYLOXY)METHYL]-2,3-DIHYDROXYHEPTADECYL}HEXACOSANAMIDE'>AGH</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[https://proteopedia.org/fgij/fg.htm?mol=4en3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4en3 OCA], [https://pdbe.org/4en3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4en3 RCSB], [https://www.ebi.ac.uk/pdbsum/4en3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4en3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CD1D_HUMAN CD1D_HUMAN] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:17475845</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases. Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Valpha24-Jalpha18 TCR rearrangements of iNKT cells, which comprise a subset of the human CD1d-restricted T cell population. In contrast, little is known about how lipid antigens are recognized by functionally distinct CD1d-restricted T cells bearing different TCRalpha chain rearrangements. Here we present crystallographic and biophysical analyses of alpha-galactosylceramide (alpha-GalCer) recognition by a human CD1d-restricted TCR that utilizes a Valpha3.1-Jalpha18 rearrangement and displays a more restricted specificity for alpha-linked glycolipids than that of iNKT TCRs. Despite having sequence divergence in the CDR1alpha and CDR2alpha loops, this TCR employs a convergent recognition strategy to engage CD1d/alphaGalCer, with a binding affinity ( approximately 2 microM) almost identical to that of an iNKT TCR used in this study. The CDR3alpha loop, similar in sequence to iNKT-TCRs, engages CD1d/alphaGalCer in a similar position as that seen with iNKT-TCRs, however fewer actual contacts are made. Instead, the CDR1alpha loop contributes important contacts to CD1d/alphaGalCer, with an emphasis on the 4'OH of the galactose headgroup. This is consistent with the inability of Valpha24- T cells to respond to alpha-glucosylceramide, which differs from alphaGalCer in the position of the 4'OH. These data illustrate how fine specificity for a lipid containing alpha-linked galactose is achieved by a TCR structurally distinct from that of iNKT cells. | |||
The molecular basis for recognition of CD1d/alpha-galactosylceramide by a human non-Valpha24 T cell receptor.,Lopez-Sagaseta J, Kung JE, Savage PB, Gumperz J, Adams EJ PLoS Biol. 2012;10(10):e1001412. doi: 10.1371/journal.pbio.1001412. Epub 2012 Oct, 23. PMID:23109910<ref>PMID:23109910</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4en3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[CD1|CD1]] | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Adams EJ]] | |||
[[Category: Lopez-Sagaseta J]] | |||