2av7
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2av7.gif|left|200px]] | + | [[Image:2av7.gif|left|200px]] |
| - | + | ||
| - | '''Crystal structure of HTLV-1 TAX peptide Bound to Human Class I MHC HLA-A2 with the K66A mutation in the heavy chain.''' | + | {{Structure |
| + | |PDB= 2av7 |SIZE=350|CAPTION= <scene name='initialview01'>2av7</scene>, resolution 2.05Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), B2M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of HTLV-1 TAX peptide Bound to Human Class I MHC HLA-A2 with the K66A mutation in the heavy chain.''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2AV7 is a [ | + | 2AV7 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AV7 OCA]. |
==Reference== | ==Reference== | ||
| - | Unraveling a hotspot for TCR recognition on HLA-A2: evidence against the existence of peptide-independent TCR binding determinants., Gagnon SJ, Borbulevych OY, Davis-Harrison RL, Baxter TK, Clemens JR, Armstrong KM, Turner RV, Damirjian M, Biddison WE, Baker BM, J Mol Biol. 2005 Oct 28;353(3):556-73. Epub 2005 Sep 2. PMID:[http:// | + | Unraveling a hotspot for TCR recognition on HLA-A2: evidence against the existence of peptide-independent TCR binding determinants., Gagnon SJ, Borbulevych OY, Davis-Harrison RL, Baxter TK, Clemens JR, Armstrong KM, Turner RV, Damirjian M, Biddison WE, Baker BM, J Mol Biol. 2005 Oct 28;353(3):556-73. Epub 2005 Sep 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16197958 16197958] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| Line 25: | Line 34: | ||
[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:54:13 2008'' |
Revision as of 13:54, 20 March 2008
| |||||||
| , resolution 2.05Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | HLA-A, HLAA (Homo sapiens), B2M (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of HTLV-1 TAX peptide Bound to Human Class I MHC HLA-A2 with the K66A mutation in the heavy chain.
Contents |
Overview
T cell receptor (TCR) recognition of peptide takes place in the context of the major histocompatibility complex (MHC) molecule, which accounts for approximately two-thirds of the peptide/MHC buried surface. Using the class I MHC HLA-A2 and a large panel of mutants, we have previously shown that surface mutations that disrupt TCR recognition vary with the identity of the peptide. The single exception is Lys66 on the HLA-A2 alpha1 helix, which when mutated to alanine disrupts recognition for 93% of over 250 different T cell clones or lines, independent of which peptide is bound. Thus, Lys66 could serve as a peptide-independent TCR binding determinant. Here, we have examined the role of Lys66 in TCR recognition of HLA-A2 in detail. The structure of a peptide/HLA-A2 molecule with the K66A mutation indicates that although the mutation induces no major structural changes, it results in the exposure of a negatively charged glutamate (Glu63) underneath Lys66. Concurrent replacement of Glu63 with glutamine restores TCR binding and function for T cells specific for five different peptides presented by HLA-A2. Thus, the positive charge on Lys66 does not serve to guide all TCRs onto the HLA-A2 molecule in a manner required for productive signaling. Furthermore, electrostatic calculations indicate that Lys66 does not contribute to the stability of two TCR-peptide/HLA-A2 complexes. Our findings are consistent with the notion that each TCR arrives at a unique solution of how to bind a peptide/MHC, most strongly influenced by the chemical and structural features of the bound peptide. This would not rule out an intrinsic affinity of TCRs for MHC molecules achieved through multiple weak interactions, but for HLA-A2 the collective mutational data place limits on the role of any single MHC amino acid side-chain in driving TCR binding in a peptide-independent fashion.
Disease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Hypoproteinemia, hypercatabolic OMIM:[109700], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this Structure
2AV7 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Unraveling a hotspot for TCR recognition on HLA-A2: evidence against the existence of peptide-independent TCR binding determinants., Gagnon SJ, Borbulevych OY, Davis-Harrison RL, Baxter TK, Clemens JR, Armstrong KM, Turner RV, Damirjian M, Biddison WE, Baker BM, J Mol Biol. 2005 Oct 28;353(3):556-73. Epub 2005 Sep 2. PMID:16197958
Page seeded by OCA on Thu Mar 20 15:54:13 2008
