Summary
PDB 3PGD deposited: 2010-11-01 modified: 2011-01-05
Title Crystal Structure of HLA-DR1 with CLIP106-120, canonical peptide orientation
Authors Falk, K., Freund, C., Gunther, S., Heinemann, U., Jung, G., Roske, Y., Rotzschke, O., Schlundt, A., Sticht, J., Wiesmuller, K.H.
Method X-RAY DIFFRACTION
Structure factors resolution 2.72 rfactor 0.196 rfree 0.2416
DPI 0.94 theoretical min: 0.42
Related PDB Entries 3PDO 3PGC
Citations

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 U S A. 2010 Dec 21;107(51):22219-24. Epub 2010 Nov 29.

Cross References
Database source Identifier Description
PubMed 21115828 PNASA6
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3PGD/1 3PGD 1 trimer 0 3 0 3018
3PGD/2 3PGD 2 trimer 0 3 0 3032