3o6f: Difference between revisions
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[[ | ==Crystal structure of a human autoimmune TCR MS2-3C8 bound to MHC class II self-ligand MBP/HLA-DR4== | ||
<StructureSection load='3o6f' size='340' side='right' caption='[[3o6f]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o6f]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O6F FirstGlance]. <br> | |||
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-DRA, HLA-DRA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HLA-DRB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TRAC, TCRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TRBC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3o6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o6f RCSB], [http://www.ebi.ac.uk/pdbsum/3o6f PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3beta conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity. | |||
Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection.,Yin Y, Li Y, Kerzic MC, Martin R, Mariuzza RA EMBO J. 2011 Feb 4. PMID:21297580<ref>PMID:21297580</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Major histocompatibility complex|Major histocompatibility complex]] | *[[Major histocompatibility complex|Major histocompatibility complex]] | ||
*[[T-cell receptor|T-cell receptor]] | |||
== | == References == | ||
< | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Li, Y | [[Category: Li, Y]] | ||
[[Category: Mariuzza, R A | [[Category: Mariuzza, R A]] | ||
[[Category: Martin, R | [[Category: Martin, R]] | ||
[[Category: Yin, Y | [[Category: Yin, Y]] | ||
[[Category: Autoimmunity]] | [[Category: Autoimmunity]] | ||
[[Category: Hla class ii]] | [[Category: Hla class ii]] | ||
Revision as of 14:50, 9 December 2014
Crystal structure of a human autoimmune TCR MS2-3C8 bound to MHC class II self-ligand MBP/HLA-DR4Crystal structure of a human autoimmune TCR MS2-3C8 bound to MHC class II self-ligand MBP/HLA-DR4
Structural highlights
Publication Abstract from PubMedThe failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3beta conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity. Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection.,Yin Y, Li Y, Kerzic MC, Martin R, Mariuzza RA EMBO J. 2011 Feb 4. PMID:21297580[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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