This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 11: | Line 10: | ||
==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== | ||
| Line 18: | Line 17: | ||
[[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]] | ||
| Line 26: | Line 25: | ||
[[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
|
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
Page seeded by OCA on Thu Feb 21 16:06:53 2008
