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==Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)== | |||
<StructureSection load='1klu' size='340' side='right'caption='[[1klu]], [[Resolution|resolution]] 1.93Å' scene=''> | |||
| | == Structural highlights == | ||
| | <table><tr><td colspan='2'>[[1klu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KLU 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]] 1.93Å</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=1klu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klu OCA], [https://pdbe.org/1klu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1klu RCSB], [https://www.ebi.ac.uk/pdbsum/1klu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1klu ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:[https://omim.org/entry/190450 190450]. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TPIS_HUMAN TPIS_HUMAN] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/1klu_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1klu ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies. | |||
Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.,Sundberg EJ, Sawicki MW, Southwood S, Andersen PS, Sette A, Mariuzza RA J Mol Biol. 2002 May 31;319(2):449-61. PMID:12051920<ref>PMID:12051920</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1klu" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[MHC 3D structures|MHC 3D structures]] | |||
*[[MHC II 3D structures|MHC II 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Andersen | [[Category: Andersen PS]] | ||
[[Category: Mariuzza | [[Category: Mariuzza RA]] | ||
[[Category: Sawicki | [[Category: Sawicki MW]] | ||
[[Category: Sette | [[Category: Sette A]] | ||
[[Category: Sidney | [[Category: Sidney J]] | ||
[[Category: Sundberg | [[Category: Sundberg EJ]] | ||
Latest revision as of 09:54, 30 October 2024
Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
Structural highlights
DiseaseTPIS_HUMAN Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:190450. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWhile most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies. Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.,Sundberg EJ, Sawicki MW, Southwood S, Andersen PS, Sette A, Mariuzza RA J Mol Biol. 2002 May 31;319(2):449-61. PMID:12051920[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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