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New page: '''Unreleased structure''' The entry 7nzf is ON HOLD Authors: Changrong, G., Doreen, D., Rikard, H. Description: Crystal structure of HLA-DR4 in complex with a mutated human collagen t...
 
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'''Unreleased structure'''


The entry 7nzf is ON HOLD
==Crystal structure of HLA-DR4 in complex with a mutated human collagen type II peptide==
<StructureSection load='7nzf' size='340' side='right'caption='[[7nzf]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nzf]] is a 3 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=7NZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NZF 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]] 1.9&#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=7nzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nzf OCA], [https://pdbe.org/7nzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nzf RCSB], [https://www.ebi.ac.uk/pdbsum/7nzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nzf ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease strongly associated with the major histocompatibility complex (MHC) class II allele DRB1*04:01, which encodes a protein that binds self-peptides for presentation to T cells. This study characterises the autoantigen-presenting function of DRB1*04:01 (HLA-DRA*01:01/HLA-DRB1*04:01) at a molecular level for prototypic T-cell determinants, focusing on a post-translationally modified collagen type II (Col2)-derived peptide. METHODS: The crystal structures of DRB1*04:01 molecules in complex with the peptides HSP70(289-306), citrullinated CILP(982-996) and galactosylated Col2(259-273) were determined on cocrystallisation. T cells specific for Col2(259-273) were investigated in peripheral blood mononuclear cells from patients with DRB1*04:01-positive RA by cytofluorometric detection of the activation marker CD154 on peptide stimulation and binding of fluorescent DRB1*0401/Col2(259-273) tetramer complexes. The cDNAs encoding the T-cell receptor (TCR) alpha-chains and beta-chains were cloned from single-cell sorted tetramer-positive T cells and transferred via a lentiviral vector into TCR-deficient Jurkat 76 cells. RESULTS: The crystal structures identified peptide binding to DRB1*04:01 and potential side chain exposure to T cells. The main TCR recognition sites in Col2(259-273) were lysine residues that can be galactosylated. RA T-cell responses to DRB1*04:01-presented Col2(259-273) were dependent on peptide galactosylation at lysine 264. Dynamic molecular modelling of a functionally characterised Col2(259-273)-specific TCR complexed with DRB1*04:01/Col2(259-273) provided evidence for differential allosteric T-cell recognition of glycosylated lysine 264. CONCLUSIONS: The MHC-peptide-TCR interactions elucidated in our study provide new molecular insights into recognition of a post-translationally modified RA T-cell determinant with a known dominant role in arthritogenic and tolerogenic responses in murine Col2-induced arthritis.


Authors: Changrong, G., Doreen, D., Rikard, H.
Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor.,Ge C, Weisse S, Xu B, Dobritzsch D, Viljanen J, Kihlberg J, Do NN, Schneider N, Lanig H, Holmdahl R, Burkhardt H Ann Rheum Dis. 2022 Apr;81(4):480-489. doi: 10.1136/annrheumdis-2021-220500. Epub , 2022 Jan 13. PMID:35027402<ref>PMID:35027402</ref>


Description: Crystal structure of HLA-DR4 in complex with a mutated human collagen type II peptide
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Changrong, G]]
<div class="pdbe-citations 7nzf" style="background-color:#fffaf0;"></div>
[[Category: Doreen, D]]
== References ==
[[Category: Rikard, H]]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Changrong G]]
[[Category: Doreen D]]
[[Category: Rikard H]]
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