1zgl
From Proteopedia
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[[Image:1zgl.gif|left|200px]] | [[Image:1zgl.gif|left|200px]] | ||
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'''Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a''' | '''Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a''' | ||
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[[Category: Martin, R.]] | [[Category: Martin, R.]] | ||
[[Category: Quandt, J A.]] | [[Category: Quandt, J A.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:35:54 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:35, 3 May 2008
Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a
Overview
Multiple sclerosis is mediated by T-cell responses to central nervous system antigens such as myelin basic protein (MBP). To investigate self-peptide/major histocompatibility complex (MHC) recognition and T-cell receptor (TCR) degeneracy, we determined the crystal structure, at 2.8 A resolution, of an autoimmune TCR (3A6) bound to an MBP self-peptide and the multiple sclerosis-associated MHC class II molecule, human leukocyte antigen (HLA)-DR2a. The complex reveals that 3A6 primarily recognizes the N-terminal portion of MBP, in contrast with antimicrobial and alloreactive TCRs, which focus on the peptide center. Moreover, this binding mode, which may be frequent among autoimmune TCRs, is compatible with a wide range of orientation angles of TCR to peptide/MHC. The interface is characterized by a scarcity of hydrogen bonds between TCR and peptide, and TCR-induced conformational changes in MBP/HLA-DR2a, which likely explain the low observed affinity. Degeneracy of 3A6, manifested by recognition of superagonist peptides bearing substitutions at nearly all TCR-contacting positions, results from the few specific interactions between 3A6 and MBP, allowing optimization of interface complementarity through variations in the peptide.
About this Structure
1ZGL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule., Li Y, Huang Y, Lue J, Quandt JA, Martin R, Mariuzza RA, EMBO J. 2005 Sep 7;24(17):2968-79. Epub 2005 Aug 4. PMID:16079912 Page seeded by OCA on Sat May 3 17:35:54 2008
