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Conformational lability in the class II MHC 310helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , |
| In: | Proceedings of the National Academy of Sciences, 108, 2011, 48, S. 19329-19334 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 3<jats:sub>10</jats:sub>helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange.</jats:p> |
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| Umfang: | 19329-19334 |
| ISSN: |
0027-8424
1091-6490 |
| DOI: | 10.1073/pnas.1108074108 |