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1xh3
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from | + | Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from an alternative reading frame of M-CSF with high affinity. Due to its extraordinary length, the exact HLA binding mode was unpredictable. The crystal structure of HLA-B*3501 at 1.5 A shows that the N and C termini of the peptide are embedded in the A and F pockets, respectively, similar to a peptide of normal length. The central part of the 14-meric peptide bulges flexibly out of the groove. Two variants of the alternative reading frame of M-CSF peptide substituted at P2 or P2 and P9 with Ala display weak or no T cell activation. Their structure differs mainly in flexibility and conformation from the agonistic peptide. Moreover, the variants induce subtle changes of MHC alpha-helical regions implicated as critical for TCR contact. The TCR specifically recognizing this peptide/MHC complex exhibits CDR3 length within the normal range, suggesting major conformational adaptations of this receptor upon peptide/MHC binding. Thus, the potential antigenic repertoire recognizable by CTLs is larger than currently thought. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Eynde, B | + | [[Category: Eynde, B J.van den.]] |
| - | [[Category: Hecht, H | + | [[Category: Hecht, H J.]] |
[[Category: Herrmann, H.]] | [[Category: Herrmann, H.]] | ||
[[Category: Janke, V.]] | [[Category: Janke, V.]] | ||
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[[Category: immune system]] | [[Category: immune system]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:42 2008'' |
Revision as of 13:54, 21 February 2008
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Conformational Restraints and Flexibility of 14-Meric Peptides in Complex with HLA-B*3501
Contents |
Overview
Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from an alternative reading frame of M-CSF with high affinity. Due to its extraordinary length, the exact HLA binding mode was unpredictable. The crystal structure of HLA-B*3501 at 1.5 A shows that the N and C termini of the peptide are embedded in the A and F pockets, respectively, similar to a peptide of normal length. The central part of the 14-meric peptide bulges flexibly out of the groove. Two variants of the alternative reading frame of M-CSF peptide substituted at P2 or P2 and P9 with Ala display weak or no T cell activation. Their structure differs mainly in flexibility and conformation from the agonistic peptide. Moreover, the variants induce subtle changes of MHC alpha-helical regions implicated as critical for TCR contact. The TCR specifically recognizing this peptide/MHC complex exhibits CDR3 length within the normal range, suggesting major conformational adaptations of this receptor upon peptide/MHC binding. Thus, the potential antigenic repertoire recognizable by CTLs is larger than currently thought.
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
1XH3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Conformational restraints and flexibility of 14-meric peptides in complex with HLA-B*3501., Probst-Kepper M, Hecht HJ, Herrmann H, Janke V, Ocklenburg F, Klempnauer J, van den Eynde BJ, Weiss S, J Immunol. 2004 Nov 1;173(9):5610-6. PMID:15494511
Page seeded by OCA on Thu Feb 21 15:54:42 2008
