2bst: Difference between revisions
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New page: left|200px<br /> <applet load="2bst" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bst, resolution 2.1Å" /> '''CRYSTAL STRUCTURES A... |
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==Overview== | ==Overview== | ||
We have solved the crystal structures of three HLA-B*2705-peptide, complexes with the immunodominant viral peptides: EBV EBNA3C 258-266, (RRIYDLIEL), influenza (flu) nucleoprotein NP383-391 (SRYWAIRTR), and HIV, gag 264-273 (KRWIILGLNK). Long-term non-progression during HIV infection, has been associated with presentation by HLA-B*2705, and T cell, recognition, of the highly immunodominant KRWIILGLNK peptide. The tight, hydrogen-bonding network observed between the HLA-B*2705 B-pocket and the, peptide P2 arginine guanadinium anchor explains why mutation of this, residue during HIV infection results in loss of peptide binding, immune, escape and progression to AIDS. Prominent, solvent-exposed structures, within these peptides may participate in generating T cell responses to, these immunodominant epitopes. In the HLA-B*2705 complex with flu, NP383-391, the amino acid side chains of residues 4, 7 and 8 are, solvent-exposed whilst in the HIV decamer, the main-chain bulges into the, solvent around P7. Thus, HLA-B*2705 presents viral peptides in a range of, conformations. Tetrameric complexes of HLA-B*2705 with the HIV and flu but, not EBV peptides bound strongly to the killer-Ig-like receptor (KIR)3DL1., Substitution of EBV P8 glutamate to threonine allowed recognition by, KIR3DL1. In the HLA-B*2705-EBV structure the P8 glutamate side chain is, solvent-exposed and may inhibit KIR3DL1 binding through electrostatic, forces. | We have solved the crystal structures of three HLA-B*2705-peptide, complexes with the immunodominant viral peptides: EBV EBNA3C 258-266, (RRIYDLIEL), influenza (flu) nucleoprotein NP383-391 (SRYWAIRTR), and HIV, gag 264-273 (KRWIILGLNK). Long-term non-progression during HIV infection, has been associated with presentation by HLA-B*2705, and T cell, recognition, of the highly immunodominant KRWIILGLNK peptide. The tight, hydrogen-bonding network observed between the HLA-B*2705 B-pocket and the, peptide P2 arginine guanadinium anchor explains why mutation of this, residue during HIV infection results in loss of peptide binding, immune, escape and progression to AIDS. Prominent, solvent-exposed structures, within these peptides may participate in generating T cell responses to, these immunodominant epitopes. In the HLA-B*2705 complex with flu, NP383-391, the amino acid side chains of residues 4, 7 and 8 are, solvent-exposed whilst in the HIV decamer, the main-chain bulges into the, solvent around P7. Thus, HLA-B*2705 presents viral peptides in a range of, conformations. Tetrameric complexes of HLA-B*2705 with the HIV and flu but, not EBV peptides bound strongly to the killer-Ig-like receptor (KIR)3DL1., Substitution of EBV P8 glutamate to threonine allowed recognition by, KIR3DL1. In the HLA-B*2705-EBV structure the P8 glutamate side chain is, solvent-exposed and may inhibit KIR3DL1 binding through electrostatic, forces. | ||
==Disease== | |||
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Spondyloarthropathy, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: viral nucleoprotein]] | [[Category: viral nucleoprotein]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:05:59 2007'' | ||
