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1xh3
From Proteopedia
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'''Conformational Restraints and Flexibility of 14-Meric Peptides in Complex with HLA-B*3501''' | '''Conformational Restraints and Flexibility of 14-Meric Peptides in Complex with HLA-B*3501''' | ||
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[[Category: Probst-Kepper, M.]] | [[Category: Probst-Kepper, M.]] | ||
[[Category: Weiss, S.]] | [[Category: Weiss, S.]] | ||
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Revision as of 12:01, 3 May 2008
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 disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]
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 Sat May 3 15:01:11 2008
