1xh3 | pdb_00001xh3
Conformational Restraints and Flexibility of 14-Meric Peptides in Complex with HLA-B*3501
|
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 Mon Nov 12 20:05:28 2007
