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==Crystal Structure of H-2D in complex with an insulin derived peptide==
==Crystal Structure of H-2D in complex with an insulin derived peptide==
<StructureSection load='3ws3' size='340' side='right' caption='[[3ws3]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
<StructureSection load='3ws3' size='340' side='right'caption='[[3ws3]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3ws3]] is a 6 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=3WS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WS3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3ws3]] is a 6 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=3WS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WS3 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ws6|3ws6]]</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]] 2.335&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H-2Db, H2-D1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3ws3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws3 OCA], [https://pdbe.org/3ws3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ws3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ws3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ws3 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=3ws3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws3 OCA], [http://pdbe.org/3ws3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ws3 RCSB], [http://www.ebi.ac.uk/pdbsum/3ws3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ws3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE]] Involved in the presentation of foreign 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.  
[https://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Self-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several beta cell-cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive beta cell-specific ligand for AI4 as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14-20). Crystallography reveals that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind sufficiently to the MHC to enable destructive T cell responses, yet allow cognate T cells to avoid negative selection. InsA14-20 shares two solvent-exposed residues with previously identified AI4 ligands, providing a structural explanation for AI4's promiscuity. Detection of AI4-like T cells, using mimotopes of InsA14-20 with improved H-2D(b)-binding characteristics, establishes the AI4-like T cell population as a consistent feature of the islet infiltrates of NOD mice. Our work establishes undersized peptides as previously unrecognized targets of autoreactive CD8 T cells and presents a strategy for their further exploration as Ags in autoimmune disease.
 
Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses.,Lamont D, Mukherjee G, Kumar PR, Samanta D, McPhee CG, Kay TW, Almo SC, DiLorenzo TP, Serreze DV J Immunol. 2014 Sep 1;193(5):2135-46. doi: 10.4049/jimmunol.1400997. Epub 2014, Jul 25. PMID:25063871<ref>PMID:25063871</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ws3" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[Beta-lactamase|Beta-lactamase]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Almo, S C]]
[[Category: Mus musculus]]
[[Category: DiLorenzo, T P]]
[[Category: Almo SC]]
[[Category: Kumar, P R]]
[[Category: DiLorenzo TP]]
[[Category: Mukherjee, G]]
[[Category: Immune Function Network]]
[[Category: Structural genomic]]
[[Category: Kumar PR]]
[[Category: Network, Immune Function]]
[[Category: Mukherjee G]]
[[Category: Samanta, D]]
[[Category: Samanta D]]
[[Category: Class i mhc]]
[[Category: H-2d]]
[[Category: Immune system]]
[[Category: Insulin]]
[[Category: Major histocompatibility complex]]
[[Category: Nysgrc]]
[[Category: Psi-biology]]

Latest revision as of 13:24, 8 November 2023

Crystal Structure of H-2D in complex with an insulin derived peptide

3ws3, resolution 2.33Å

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