1sys
From Proteopedia
(New page: 200px<br /> <applet load="1sys" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sys, resolution 2.4Å" /> '''Crystal structure of...) |
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| - | [[Image:1sys.gif|left|200px]]<br /> | + | [[Image:1sys.gif|left|200px]]<br /><applet load="1sys" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1sys" size=" | + | |
caption="1sys, resolution 2.4Å" /> | caption="1sys, resolution 2.4Å" /> | ||
'''Crystal structure of HLA, B*4403, and peptide EEPTVIKKY'''<br /> | '''Crystal structure of HLA, B*4403, and peptide EEPTVIKKY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | HLA class I polymorphism creates diversity in epitope specificity and T | + | HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SYS 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:// | + | 1SYS 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=1SYS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Beddoe, T.]] | [[Category: Beddoe, T.]] | ||
| - | [[Category: Bottomley, S | + | [[Category: Bottomley, S P.]] |
| - | [[Category: Brooks, A | + | [[Category: Brooks, A G.]] |
[[Category: Crockford, T.]] | [[Category: Crockford, T.]] | ||
| - | [[Category: Ely, L | + | [[Category: Ely, L K.]] |
[[Category: Holdsworth, R.]] | [[Category: Holdsworth, R.]] | ||
[[Category: Kjer-Nielsen, L.]] | [[Category: Kjer-Nielsen, L.]] | ||
[[Category: Laham, N.]] | [[Category: Laham, N.]] | ||
| - | [[Category: Macdonald, W | + | [[Category: Macdonald, W A.]] |
[[Category: McCluskey, J.]] | [[Category: McCluskey, J.]] | ||
| - | [[Category: Mifsud, N | + | [[Category: Mifsud, N A.]] |
| - | [[Category: Peh, C | + | [[Category: Peh, C A.]] |
| - | [[Category: Purcell, A | + | [[Category: Purcell, A W.]] |
[[Category: Rossjohn, J.]] | [[Category: Rossjohn, J.]] | ||
| - | [[Category: Tait, B | + | [[Category: Tait, B D.]] |
[[Category: Zernich, D.]] | [[Category: Zernich, D.]] | ||
[[Category: b44]] | [[Category: b44]] | ||
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[[Category: mhc]] | [[Category: mhc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:07:24 2008'' |
Revision as of 13:07, 21 February 2008
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Crystal structure of HLA, B*4403, and peptide EEPTVIKKY
Contents |
Overview
HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.
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
1SYS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion., Zernich D, Purcell AW, Macdonald WA, Kjer-Nielsen L, Ely LK, Laham N, Crockford T, Mifsud NA, Bharadwaj M, Chang L, Tait BD, Holdsworth R, Brooks AG, Bottomley SP, Beddoe T, Peh CA, Rossjohn J, McCluskey J, J Exp Med. 2004 Jul 5;200(1):13-24. Epub 2004 Jun 28. PMID:15226359
Page seeded by OCA on Thu Feb 21 15:07:24 2008
Categories: Homo sapiens | Protein complex | Beddoe, T. | Bottomley, S P. | Brooks, A G. | Crockford, T. | Ely, L K. | Holdsworth, R. | Kjer-Nielsen, L. | Laham, N. | Macdonald, W A. | McCluskey, J. | Mifsud, N A. | Peh, C A. | Purcell, A W. | Rossjohn, J. | Tait, B D. | Zernich, D. | B44 | Class i | Hla | Mhc
