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1ymm
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= HLA-DRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HLA-DRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ymm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ymm OCA], [http://www.ebi.ac.uk/pdbsum/1ymm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ymm RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545 154545]], Diabetes mellitus, gestational, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545 154545]], Mannose-binding protein deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545 154545]], Meningococcal disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154545 154545]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Pyrdol, J.]] | [[Category: Pyrdol, J.]] | ||
[[Category: Wucherpfennig, K W.]] | [[Category: Wucherpfennig, K W.]] | ||
| - | [[Category: NAG]] | ||
[[Category: auto-immunity]] | [[Category: auto-immunity]] | ||
[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
[[Category: t cell repertoire]] | [[Category: t cell repertoire]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:13:19 2008'' |
Revision as of 22:13, 30 March 2008
| |||||||
| , resolution 3.500Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | HLA-DRA (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
TCR/HLA-DR2b/MBP-peptide complex
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.
About this Structure
1YMM is a Protein complex structure of sequences from Homo sapiens. 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 Mon Mar 31 01:13:19 2008
