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4wuu
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Structure of ESK1 in complex with HLA-A*0201/WT1== |
| + | <StructureSection load='4wuu' size='340' side='right' caption='[[4wuu]], [[Resolution|resolution]] 3.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4wuu]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WUU FirstGlance]. <br> | ||
| + | </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=4wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wuu OCA], [http://pdbe.org/4wuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wuu RCSB], [http://www.ebi.ac.uk/pdbsum/4wuu PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Antibody therapies currently target only extracellular antigens. A strategy to recognize intracellular antigens is to target peptides presented by immune HLA receptors. ESK1 is a human, T-cell receptor (TCR)-mimic antibody that binds with sub-nanomolar affinity to the RMF peptide from the intracellular oncoprotein Wilms Tumor 1 (WT1) in complex with HLA-A*02:01. ESK1 is therapeutically effective in mouse models of WT1+ human cancers. TCR-based therapies have been presumed to be restricted to one HLA subtype. The mechanism for the specificity and high affinity of ESK1 is unknown. We show in a crystal structure that ESK1 Fab binds to RMF/HLA-A*02:01 in a different mode than TCRs. From the structure, we predict and then experimentally confirm high affinity binding with multiple other HLA-A*02 subtypes, broadening the potential patient pool for ESK1 therapy. Using the crystal structure, we also predict potential off-target binding that we experimentally confirm. Our results demonstrate how protein structure information can contribute to personalized immunotherapy. | ||
| - | + | Structure of a TCR mimic antibody with target predicts pharmacogenetics.,Ataie N, Xiang J, Cheng N, Brea EJ, Lu W, Scheinberg DA, Liu C, Ng HL J Mol Biol. 2015 Dec 11. pii: S0022-2836(15)00691-9. doi:, 10.1016/j.jmb.2015.12.002. PMID:26688548<ref>PMID:26688548</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 4wuu" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Ataie, N J]] | ||
| + | [[Category: Ng, H L]] | ||
| + | [[Category: Antibody]] | ||
| + | [[Category: Hla-a*0201]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Mhc 1]] | ||
| + | [[Category: Wt1]] | ||
Revision as of 19:26, 30 December 2015
Structure of ESK1 in complex with HLA-A*0201/WT1
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Categories: Ataie, N J | Ng, H L | Antibody | Hla-a*0201 | Immune system | Mhc 1 | Wt1
