6c5m: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6c5m is ON HOLD  until Paper Publication
+==Structure of glycolipid aGSA[8,9] in complex with mouse CD1d==
+<StructureSection load='6c5m' size='340' side='right'caption='[[6c5m]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6c5m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C5M 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]] 2.45&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=J81:(5~{R},6~{S},7~{S})-8-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-~{N}-nonyl-7-(octanoylamino)-5,6-bis(oxidanyl)octanamide'>J81</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=6c5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c5m OCA], [https://pdbe.org/6c5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c5m RCSB], [https://www.ebi.ac.uk/pdbsum/6c5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c5m ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CD1D1_MOUSE CD1D1_MOUSE] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:11754812</ref> <ref>PMID:16314439</ref> <ref>PMID:16007091</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Type I Natural Killer T (NKT) cells are a population of innate like T lymphocytes that rapidly respond to alpha-GalCer presented by CD1d, via the production of both pro and anti-inflammatory cytokines. While developing novel alpha-GalCer analogs that were meant to be utilized as potential adjuvants due to their production of pro-inflammatory cytokines (Th1 skewers), we generated alpha-galactosylsphingamides (alpha-GSA). Surprisingly, alpha-GSAs are not potent antigens in vivodespite their strong T-cell receptor (TCR)-binding affinities. Here, using surface plasmon resonance (SPR), antigen presentation assays, and X-ray crystallography (yielding crystal structures of 19 different binary [CD1d-glycolipid] or ternary [CD1d-glycolipid-TCR] complexes at resolutions between 1.67 and 2.85 A), we characterized the biochemical and structural details of alpha-GSA recognition by murine NKT cells. We identified a molecular switch within murine (m)CD1d that modulates NKT cell activation by alpha-GSAs. We found that the molecular switch involves a hydrogen bond interaction between Tyr-73 of mCD1d and the amide group oxygen of alpha-GSAs. We further established that the length of the acyl chain controls the positioning of the amide group with respect to the molecular switch and works synergistically with Tyr-73 to control NKT cell activity. In conclusion, our findings reveal important mechanistic insights into the presentation and recognition of glycolipids with polar moieties in an otherwise apolar milieu.These observations may inform the development alpha-GSAs as specific NKT cell antagonists to modulate immune responses.
-Authors: Zajonc, D.M., Wang, J.
+A molecular switch in mouse CD1d modulates natural killer T cell activation by alpha-galactosylsphingamides.,Wang J, Guillaume J, Janssens J, Remesh SG, Ying G, Bitra A, Van Calenbergh S, Zajonc DM J Biol Chem. 2019 Aug 7. pii: RA119.009963. doi: 10.1074/jbc.RA119.009963. PMID:31391251<ref>PMID:31391251</ref>
-Description: Structure of glycolipid aGSA[8,9] in complex with mouse CD1d
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Zajonc, D.M]]
+<div class="pdbe-citations 6c5m" style="background-color:#fffaf0;"></div>
-[[Category: Wang, J]]
+==See Also==
+*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
+*[[CD1|CD1]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Wang J]]
+[[Category: Zajonc DM]]