1s8d
From Proteopedia
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| - | [[Image:1s8d.gif|left|200px]]<br /> | + | [[Image:1s8d.gif|left|200px]]<br /><applet load="1s8d" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1s8d" size=" | + | |
caption="1s8d, resolution 2.20Å" /> | caption="1s8d, resolution 2.20Å" /> | ||
'''Structural basis for degenerate recognition of HIV peptide variants by cytotoxic lymphocyte, variant SL9-3A'''<br /> | '''Structural basis for degenerate recognition of HIV peptide variants by cytotoxic lymphocyte, variant SL9-3A'''<br /> | ||
==Overview== | ==Overview== | ||
| - | It is well established that even small changes in amino acid side chains | + | It is well established that even small changes in amino acid side chains of antigenic peptide bound to major histocompatibility complex (MHC) protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T cell receptor (TCR). Often, however, several nonconservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein. High resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1S8D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1S8D is a [http://en.wikipedia.org/wiki/Protein_complex 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=1S8D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Anikeeva, N.]] | [[Category: Anikeeva, N.]] | ||
| - | [[Category: Hendrickson, W | + | [[Category: Hendrickson, W A.]] |
| - | [[Category: Kalams, S | + | [[Category: Kalams, S A.]] |
[[Category: Martinez-Hackert, E.]] | [[Category: Martinez-Hackert, E.]] | ||
[[Category: Sykulev, Y.]] | [[Category: Sykulev, Y.]] | ||
| - | [[Category: Walker, B | + | [[Category: Walker, B D.]] |
[[Category: ctl]] | [[Category: ctl]] | ||
[[Category: cytotoxic t lymphocytes]] | [[Category: cytotoxic t lymphocytes]] | ||
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[[Category: tcr]] | [[Category: tcr]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:02 2008'' |
Revision as of 12:59, 21 February 2008
|
Structural basis for degenerate recognition of HIV peptide variants by cytotoxic lymphocyte, variant SL9-3A
Contents |
Overview
It is well established that even small changes in amino acid side chains of antigenic peptide bound to major histocompatibility complex (MHC) protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T cell receptor (TCR). Often, however, several nonconservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein. High resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals.
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
1S8D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes., Martinez-Hackert E, Anikeeva N, Kalams SA, Walker BD, Hendrickson WA, Sykulev Y, J Biol Chem. 2006 Jul 21;281(29):20205-12. Epub 2006 May 15. PMID:16702212
Page seeded by OCA on Thu Feb 21 14:59:02 2008
Categories: Homo sapiens | Protein complex | Anikeeva, N. | Hendrickson, W A. | Kalams, S A. | Martinez-Hackert, E. | Sykulev, Y. | Walker, B D. | Ctl | Cytotoxic t lymphocytes | Hiv | Human immunodeficiency virus | Major histocompatibility complex | Mhc | Peptide-mhc complex | Pmhc | Rmsd | Root-mean-squared deviation | Simian immunodeficiency virus | Siv | T-cell receptor | Tcr
