6cx7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6cx7' size='340' side='right'caption='[[6cx7]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='6cx7' size='340' side='right'caption='[[6cx7]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cx7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CX7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6cx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CX7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ELM:N-[(2S,3S,4R)-3,4-dihydroxy-8-oxo-8-[(6-phenylhexyl)amino]-1-{[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}octan-2-yl]dodecanamide'>ELM</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ELM:N-[(2S,3S,4R)-3,4-dihydroxy-8-oxo-8-[(6-phenylhexyl)amino]-1-{[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}octan-2-yl]dodecanamide'>ELM</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1d1, mCG_3074 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cx7 OCA], [http://pdbe.org/6cx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6cx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cx7 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cx7 OCA], [http://pdbe.org/6cx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6cx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cx7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | ||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6cx7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Wang, J]] | [[Category: Wang, J]] | ||
[[Category: Zajonc, D]] | [[Category: Zajonc, D]] | ||
Revision as of 10:05, 16 October 2019
Structure of alpha-GSA[12,6P] bound by CD1d and in complex with the Va14Vb8.2 TCRStructure of alpha-GSA[12,6P] bound by CD1d and in complex with the Va14Vb8.2 TCR
Structural highlights
Function[B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMedType 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||