1ymm
From Proteopedia
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| , resolution 3.500Å | |||||||
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| Ligands: | |||||||
| Gene: | HLA-DRA (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Mar 20 15:24:50 2008
