PDB 3PGC deposited: 2010-11-01 modified: 2011-01-05
Title Crystal Structure of HLA-DR1 with CLIP106-120, flipped peptide orientation
Authors Falk, K., Freund, C., Gunther, S., Heinemann, U., Jung, G., Roske, Y., Rotzschke, O., Schlundt, A., Sticht, J., Wiesmuller, K.H.
Structure factors resolution 2.66 rfactor 0.1983 rfree 0.2501
DPI 0.93 theoretical min: 0.41
Related PDB Entries 3PDO 3PGD

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.

Proc.Natl.Acad.Sci.USA 2010 Dec; 107(51):22219-22224 doi:10.1073/pnas.1014708107

Cross References
Database source Identifier Description
PubMed 21115828 PNASA6
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3PGC/1 3PGC 1 trimer 0 3 0 2942
3PGC/2 3PGC 2 trimer 0 3 2 2987