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| | ==Crystal structure of the mouse CD1d-C20:2-aGalCer-L363 mAb Fab complex== | | ==Crystal structure of the mouse CD1d-C20:2-aGalCer-L363 mAb Fab complex== |
| - | <StructureSection load='3ubx' size='340' side='right' caption='[[3ubx]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='3ubx' size='340' side='right'caption='[[3ubx]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ubx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ubx]] is a 8 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=3UBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=09N:(11Z,14Z)-N-[(2S,3S,4R)-1-(ALPHA-D-GALACTOPYRANOSYLOXY)-3,4-DIHYDROXYOCTADECAN-2-YL]ICOSA-11,14-DIENAMIDE'>09N</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 3.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1.1, CD1d, Cd1d1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m, CD1d ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=09N:(11Z,14Z)-N-[(2S,3S,4R)-1-(ALPHA-D-GALACTOPYRANOSYLOXY)-3,4-DIHYDROXYOCTADECAN-2-YL]ICOSA-11,14-DIENAMIDE'>09N</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ubx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubx OCA], [http://pdbe.org/3ubx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ubx RCSB], [http://www.ebi.ac.uk/pdbsum/3ubx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubx ProSAT]</span></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=3ubx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubx OCA], [https://pdbe.org/3ubx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ubx RCSB], [https://www.ebi.ac.uk/pdbsum/3ubx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | *[[CD1|CD1]] | | *[[CD1|CD1]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Yu, E D]] | + | [[Category: Yu ED]] |
| - | [[Category: Zajonc, D M]] | + | [[Category: Zajonc DM]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunology]]
| + | |
| - | [[Category: Mab]]
| + | |
| - | [[Category: Mouse cd1d/nkt]]
| + | |
| Structural highlights
Function
CD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3]
Publication Abstract from PubMed
Natural killer T (NKT) cells express a semi-invariant Valpha14 T cell receptor (TCR) and recognize structurally diverse antigens presented by the antigen-presenting molecule CD1d that range from phosphoglycerolipids to alpha- and beta-anomeric glycosphingolipids, as well as microbial alpha-glycosyl diacylglycerolipids. Recently developed antibodies that are specific for the complex of the prototypical invariant NKT (iNKT) cell antigen alphaGalCer (KRN7000) bound to mouse CD1d have become valuable tools in elucidating the mechanism of antigen loading and presentation. Here, we report the 3.1 A resolution crystal structure of the Fab of one of these antibodies, L363, bound to mCD1d complexed with the alphaGalCer analog C20:2, revealing that L363 is an iNKT TCR-like antibody that binds CD1d-presented alphaGalCer in a manner similar to the TCR. The structure reveals that L363 depends on both the L and H chains for binding to the glycolipid-mCD1d complex, although only the L chain is involved in contacts with the glycolipid antigen. The H chain of L363 features residue Trp-104, which mimics the TCR CDR3alpha residue Leu-99, which is crucial for CD1d binding. We characterized the antigen-specificity of L363 toward several different glycolipids, demonstrating that whereas the TCR can induce structural changes in both antigen and CD1d to recognize disparate lipid antigens, the antibody L363 can only induce the F' roof formation in CD1d but fails to reorient the glycolipid headgroup necessary for binding. In summary, L363 is a powerful tool to study mechanism of iNKT cell activation for structural analogs of KRN7000, and our study can aid in the design of antibodies with altered antigen specificity.
Structural basis for the recognition of C20:2-alphaGalCer by the invariant natural killer T cell receptor-like antibody L363.,Yu ED, Girardi E, Wang J, Mac TT, Yu KO, Van Calenbergh S, Porcelli SA, Zajonc DM J Biol Chem. 2012 Jan 6;287(2):1269-78. Epub 2011 Nov 22. PMID:22110136[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity. 2001 Dec;15(6):897-908. PMID:11754812
- ↑ Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439 doi:10.1084/jem.20051625
- ↑ Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005 Aug;6(8):810-8. Epub 2005 Jul 10. PMID:16007091 doi:10.1038/ni1224
- ↑ Yu ED, Girardi E, Wang J, Mac TT, Yu KO, Van Calenbergh S, Porcelli SA, Zajonc DM. Structural basis for the recognition of C20:2-alphaGalCer by the invariant natural killer T cell receptor-like antibody L363. J Biol Chem. 2012 Jan 6;287(2):1269-78. Epub 2011 Nov 22. PMID:22110136 doi:10.1074/jbc.M111.308783
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