spacer Crystal Structure of HLA-DR1 with CLIP106-120, flipped peptide orientation
Primary citation
Title Bidirectional binding of invariant chain peptides to an MHC class II molecule.
Authors Gunther,; Schlundt,; Sticht,; Roske,; Heinemann,; Wiesmuller,; Jung,; Falk,; Rotzschke,; Freund,
Journal PROC.NATL.ACAD.SCI.USAsearch vol:107, pag:22219-22224 (2010), Identifiers: PubMed ID (21115828)search DOI (10.1073/pnas.1014708107)
Abstract T-cell recognition of peptides bound to MHC class II (MHCII) molecules is a central event in cell-mediated adaptive immunity. The current paradigm holds that prebound class II-associated invariant chain peptides (CLIP) and all subsequent antigens maintain a canonical orientation in the MHCII binding groove. Here we provide evidence for MHCII-bound CLIP inversion. NMR spectroscopy demonstrates that the interconversion from the canonical to the inverse alignment is a dynamic process, and X-ray crystallography shows that conserved MHC residues form a hydrogen bond network with the peptide backbone in both orientations. The natural catalyst HLA-DM accelerates peptide reorientation and the exchange of either canonically or inversely bound CLIP against antigenic peptide. Thus, noncanonical MHC-CLIP displays the hallmarks of a structurally and functionally intact antigen-presenting complex.
MeSH terms Antigenssearch, Differentiationsearch, B-Lymphocytesearch, Crystallographysearch, X-Raysearch, HLA-DR1 Antigensearch, Histocompatibility Antigens Class IIsearch, Humanssearch, Nuclear Magnetic Resonancesearch, Biomolecularsearch, Protein Bindingsearch, Protein Structuresearch, Quaternarysearch, Structure-Activity Relationshipsearch
Other entries described in this publication 3pgd, 3pdo