1ymm
From Proteopedia
(New page: 200px<br /> <applet load="1ymm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ymm, resolution 3.500Å" /> '''TCR/HLA-DR2b/MBP-p...) |
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| - | [[Image:1ymm.gif|left|200px]]<br /> | + | [[Image:1ymm.gif|left|200px]]<br /><applet load="1ymm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ymm" size=" | + | |
caption="1ymm, resolution 3.500Å" /> | caption="1ymm, resolution 3.500Å" /> | ||
'''TCR/HLA-DR2b/MBP-peptide complex'''<br /> | '''TCR/HLA-DR2b/MBP-peptide complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Autoimmune diseases are caused by self-reactive lymphocytes that have | + | Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different from that of antimicrobial TCRs. Rather than being centered on the peptide-major histocompatibility complex, this TCR contacted only the N-terminal peptide segment and made asymmetrical interactions with the major histocompatibility complex helices. The interaction was dominated by the hypervariable complementarity-determining region 3 loops, indicating that unconventional topologies are possible because of the unique complementarity-determining region 3 sequences created during rearrangement. This topology reduces the interaction surface with peptide and alters the geometry for CD4 association. We propose that unusual TCR-binding properties can permit autoreactive T cells to escape deletion. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YMM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YMM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YMM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Hahn, M.]] | [[Category: Hahn, M.]] | ||
| - | [[Category: Nicholson, M | + | [[Category: Nicholson, M J.]] |
[[Category: Pyrdol, J.]] | [[Category: Pyrdol, J.]] | ||
| - | [[Category: Wucherpfennig, K | + | [[Category: Wucherpfennig, K W.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: auto-immunity]] | [[Category: auto-immunity]] | ||
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[[Category: t cell repertoire]] | [[Category: t cell repertoire]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:06:53 2008'' |
Revision as of 14:06, 21 February 2008
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TCR/HLA-DR2b/MBP-peptide complex
Contents |
Overview
Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different from that of antimicrobial TCRs. Rather than being centered on the peptide-major histocompatibility complex, this TCR contacted only the N-terminal peptide segment and made asymmetrical interactions with the major histocompatibility complex helices. The interaction was dominated by the hypervariable complementarity-determining region 3 loops, indicating that unconventional topologies are possible because of the unique complementarity-determining region 3 sequences created during rearrangement. This topology reduces the interaction surface with peptide and alters the geometry for CD4 association. We propose that unusual TCR-binding properties can permit autoreactive T cells to escape deletion.
Disease
Known diseases associated with this structure: Chronic infections, due to MBL deficiency OMIM:[154545], Diabetes mellitus, gestational, susceptibility to OMIM:[154545], Mannose-binding protein deficiency OMIM:[154545], Meningococcal disease, susceptibility to OMIM:[154545]
About this Structure
1YMM is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor., Hahn M, Nicholson MJ, Pyrdol J, Wucherpfennig KW, Nat Immunol. 2005 May;6(5):490-6. Epub 2005 Apr 10. PMID:15821740
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