1agf
From Proteopedia
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| - | [[Image:1agf.gif|left|200px]]<br /> | + | [[Image:1agf.gif|left|200px]]<br /><applet load="1agf" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1agf" size=" | + | |
caption="1agf, resolution 2.2Å" /> | caption="1agf, resolution 2.2Å" /> | ||
'''ANTAGONIST HIV-1 GAG PEPTIDES INDUCE STRUCTURAL CHANGES IN HLA B8-HIV-1 GAG PEPTIDE (GGKKRYKL-5R MUTATION)'''<br /> | '''ANTAGONIST HIV-1 GAG PEPTIDES INDUCE STRUCTURAL CHANGES IN HLA B8-HIV-1 GAG PEPTIDE (GGKKRYKL-5R MUTATION)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In the cellular immune response, recognition by CTL-TCRs of viral antigens | + | In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959-968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541-1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8-restricted HIV-1 P17 (aa 24-31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403-407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24-31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1AGF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http:// | + | 1AGF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bell, J.]] | [[Category: Bell, J.]] | ||
| - | [[Category: Callaghan, C | + | [[Category: Callaghan, C A.O.]] |
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
| - | [[Category: Jakobsen, B | + | [[Category: Jakobsen, B K.]] |
| - | [[Category: Jones, E | + | [[Category: Jones, E Y.]] |
[[Category: Klenerman, P.]] | [[Category: Klenerman, P.]] | ||
[[Category: Mcadam, S.]] | [[Category: Mcadam, S.]] | ||
| - | [[Category: Mcmichael, A | + | [[Category: Mcmichael, A J.]] |
| - | [[Category: Reid, S | + | [[Category: Reid, S W.]] |
| - | [[Category: Smith, K | + | [[Category: Smith, K J.]] |
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
[[Category: histocompatibility complex]] | [[Category: histocompatibility complex]] | ||
[[Category: hiv]] | [[Category: hiv]] | ||
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[[Category: mhc class i]] | [[Category: mhc class i]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:44:13 2008'' |
Revision as of 09:44, 21 February 2008
|
ANTAGONIST HIV-1 GAG PEPTIDES INDUCE STRUCTURAL CHANGES IN HLA B8-HIV-1 GAG PEPTIDE (GGKKRYKL-5R MUTATION)
Contents |
Overview
In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959-968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541-1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8-restricted HIV-1 P17 (aa 24-31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403-407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24-31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition.
Disease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this Structure
1AGF is a Protein complex structure of sequences from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Antagonist HIV-1 Gag peptides induce structural changes in HLA B8., Reid SW, McAdam S, Smith KJ, Klenerman P, O'Callaghan CA, Harlos K, Jakobsen BK, McMichael AJ, Bell JI, Stuart DI, Jones EY, J Exp Med. 1996 Dec 1;184(6):2279-86. PMID:8976183
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