View source for 5ujt


==Crystal structure of human HLA-DQ8 in complex with insulin mimotope binding in register 3==
<StructureSection load='5ujt' size='340' side='right'caption='[[5ujt]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ujt]] is a 9 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=5UJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UJT 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]] 1.94&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=5ujt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ujt OCA], [https://pdbe.org/5ujt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ujt RCSB], [https://www.ebi.ac.uk/pdbsum/5ujt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ujt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5Y7C3_HUMAN Q5Y7C3_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A polymorphism at beta57 in some major histocompatibility complex class II (MHCII) alleles of rodents and humans is associated with a high risk for developing type 1 diabetes (T1D). However, a highly diabetogenic insulin B chain epitope within the B:9-23 peptide is presented poorly by these alleles to a variety of mouse and human CD4 T cells isolated from either nonobese diabetic (NOD) mice or humans with T1D. We have shown for both species that mutations at the C-terminal end of this epitope dramatically improve presentation to these T cells. Here we present the crystal structures of these mutated peptides bound to mouse IA(g7) and human HLA-DQ8 that show how the mutations function to improve T-cell activation. In both peptide binding grooves, the mutation of B:22R to E in the peptide changes a highly unfavorable side chain for the p9 pocket to an optimal one that is dependent on the beta57 polymorphism, accounting for why these peptides bind much better to these MHCIIs. Furthermore, a second mutation of the adjacent B:21 (E to G) removes a side chain from the surface of the complex that is highly unfavorable for a subset of NOD mouse CD4 cells, thereby greatly enhancing their response to the complex. These results point out the similarities between the mouse and human responses to this B chain epitope in T1D and suggest there may be common posttranslational modifications at the C terminus of the peptide in vivo to create the pathogenic epitopes in both species.

C-terminal modification of the insulin B:11-23 peptide creates superagonists in mouse and human type 1 diabetes.,Wang Y, Sosinowski T, Novikov A, Crawford F, Neau DB, Yang J, Kwok WW, Marrack P, Kappler JW, Dai S Proc Natl Acad Sci U S A. 2017 Dec 18. pii: 1716527115. doi:, 10.1073/pnas.1716527115. PMID:29255035<ref>PMID:29255035</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ujt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dai S]]
[[Category: Wang Y]]