1XH3

Conformational Restraints and Flexibility of 14-Meric Peptides in Complex with HLA-B*3501

Summary for 1XH3

• Entry DOI: 10.2210/pdb1xh3/pdb
• Descriptor: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, aa 4-17 (LPAVVGLSPGEQEY) of alternative reading frame of M-CSF, ... (4 entities in total)
• Functional Keywords: immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30685; Secreted: P61769
• Total number of polymer chains: 3
• Total formula weight: 45147.02

Authors

Probst-Kepper, M.,Hecht, H.J.,Herrmann, H.,Janke, V.,Ocklenburg, F.,Klempnauer, J.,van den Eynde, B.J.,Weiss, S. (deposition date: 2004-09-17, release date: 2004-11-23, Last modification date: 2024-10-30)

Primary citation

Probst-Kepper, M.,Hecht, H.J.,Herrmann, H.,Janke, V.,Ocklenburg, F.,Klempnauer, J.,van den Eynde, B.J.,Weiss, S.
Conformational restraints and flexibility of 14-meric peptides in complex with HLA-B*3501.
J.Immunol., 173:5610-5616, 2004

PubMed Abstract: 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.

PubMed: 15494511

Experimental method

X-RAY DIFFRACTION (1.48 Å)