7z50
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7z50]] is a 10 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=7Z50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z50 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7z50]] is a 10 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=7Z50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z50 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.65Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[https://proteopedia.org/fgij/fg.htm?mol=7z50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z50 OCA], [https://pdbe.org/7z50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z50 RCSB], [https://www.ebi.ac.uk/pdbsum/7z50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z50 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=7z50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z50 OCA], [https://pdbe.org/7z50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z50 RCSB], [https://www.ebi.ac.uk/pdbsum/7z50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z50 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [[https://www.uniprot.org/uniprot/HA2D_MOUSE HA2D_MOUSE]] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-A(g7)-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-A(g7) complex, both in isolation as well as bound to the 4.1-TCR. We find that HIP promiscuity of the 4.1-TCR is dictated, on the one hand, by an amino acid sequence pattern that ensures I-A(g7) binding and, on the other hand, by the presence of three acidic residues at positions P5, P7 and P8 that favor an optimal engagement by the 4.1-TCR's complementary determining regions. Surprisingly, comparison of the TCR-bound and unbound HIP/I-A(g7) structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-A(g7) molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-A(g7) molecule is structurally malleable and that this plasticity allows the recognition of multiple peptides by individual TCRs that would otherwise be unable to do so. | We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-A(g7)-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-A(g7) complex, both in isolation as well as bound to the 4.1-TCR. We find that HIP promiscuity of the 4.1-TCR is dictated, on the one hand, by an amino acid sequence pattern that ensures I-A(g7) binding and, on the other hand, by the presence of three acidic residues at positions P5, P7 and P8 that favor an optimal engagement by the 4.1-TCR's complementary determining regions. Surprisingly, comparison of the TCR-bound and unbound HIP/I-A(g7) structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-A(g7) molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-A(g7) molecule is structurally malleable and that this plasticity allows the recognition of multiple peptides by individual TCRs that would otherwise be unable to do so. | ||
| - | Structural plasticity in I-A(g7) links autoreactivity to hybrid insulin peptides in type I diabetes.,Erausquin E, Serra P, Parras D, Santamaria P, Lopez-Sagaseta J Front Immunol. 2022 Jul 28;13:924311. doi: 10.3389/fimmu.2022.924311. eCollection, 2022. PMID:35967292<ref>PMID:35967292</ref> | + | Structural plasticity in I-A(g7) links autoreactivity to hybrid insulin peptides in type I diabetes.,Erausquin E, Serra P, Parras D, Santamaria P, Lopez-Sagaseta J Front Immunol. 2022 Jul 28;13:924311. doi: 10.3389/fimmu.2022.924311. eCollection , 2022. PMID:35967292<ref>PMID:35967292</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7z50" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7z50" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structure of the highly diabetogenic 4.1-T cell receptor targeting a hybrid insulin peptide bound to I-Ag7.
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