View source for 7kp0


==CD1a-42:1 SM binary complex==
<StructureSection load='7kp0' size='340' side='right'caption='[[7kp0]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kp0]] is a 2 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=7KP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KP0 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=WUA:(4R,7S)-4-hydroxy-7-[(1S,2E)-1-hydroxyhexadec-2-en-1-yl]-N,N,N-trimethyl-4,9-dioxo-3,5-dioxa-8-aza-4lambda~5~-phosphadotriacontan-1-aminium'>WUA</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=7kp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kp0 OCA], [https://pdbe.org/7kp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kp0 RCSB], [https://www.ebi.ac.uk/pdbsum/7kp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kp0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD1A_HUMAN CD1A_HUMAN] Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:11231314</ref> <ref>PMID:16272286</ref> <ref>PMID:18178838</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We optimized lipidomics methods to broadly detect endogenous lipids bound to cellular CD1a proteins. Whereas membrane phospholipids dominate in cells, CD1a preferentially captured sphingolipids, especially a C42, doubly unsaturated sphingomyelin (42:2 SM). The natural 42:2 SM but not the more common 34:1 SM blocked CD1a tetramer binding to T cells in all human subjects tested. Thus, cellular CD1a selectively captures a particular endogenous lipid that broadly blocks its binding to TCRs. Crystal structures show that the short cellular SMs stabilized a triad of surface residues to remain flush with CD1a, but the longer lipids forced the phosphocholine group to ride above the display platform to hinder TCR approach. Whereas nearly all models emphasize antigen-mediated T cell activation, we propose that the CD1a system has intrinsic autoreactivity and is negatively regulated by natural endogenous inhibitors selectively bound in its cleft. Further, the detailed chemical structures of natural blockers could guide future design of therapeutic blockers of CD1a response.

CD1a selectively captures endogenous cellular lipids that broadly block T cell response.,Cotton RN, Wegrecki M, Cheng TY, Chen YL, Veerapen N, Le Nours J, Orgill DP, Pomahac B, Talbot SG, Willis R, Altman JD, de Jong A, Van Rhijn I, Clark RA, Besra GS, Ogg G, Rossjohn J, Moody DB J Exp Med. 2021 Jul 5;218(7):e20202699. doi: 10.1084/jem.20202699. Epub 2021 May , 7. PMID:33961028<ref>PMID:33961028</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kp0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[CD1|CD1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Le Nours J]]
[[Category: Rossjohn J]]
[[Category: Wegrecki M]]