The Structure of a Peptide-Loaded Shark MHC Class I Molecule Reveals Features of the Binding between β2-Microglobulin and H Chain Conserved in Evolution
In: The Journal of Immunology, Jg. 207 (2021-07-01), S. 308-321
Online
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Zugriff:
Cartilaginous fish are the most primitive extant species with MHC molecules. Using the nurse shark, the current study is, to the best of our knowledge, the first to present a peptide-loaded MHC class I (pMHC-I) structure for this class of animals. The overall structure was found to be similar between cartilaginous fish and bony animals, showing remarkable conservation of interactions between the three pMHC-I components H chain, β2-microglobulin (β2-m), and peptide ligand. In most previous studies, relatively little attention was given to the details of binding between the H chain and β2-m, and our study provides important new insights. A pronounced conserved feature involves the insertion of a large β2-m F56+W60 hydrophobic knob into a pleat of the β-sheet floor of the H chain α1α2 domain, with the knob being surrounded by conserved residues. Another conserved feature is a hydrogen bond between β2-m Y10 and a proline in the α3 domain of the H chain. By alanine substitution analysis, we found that the conserved β2-m residues Y10, D53, F56, and W60—each binding the H chain—are required for stable pMHC-I complex formation. For the β2-m residues Y10 and F56, such observations have not been reported before. The combined data indicate that for stable pMHC-I complex formation β2-m should not only bind the α1α2 domain but also the α3 domain. Knowing the conserved structural features of pMHC-I should be helpful for future elucidations of the mechanisms of pMHC-I complex formation and peptide editing.
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The Structure of a Peptide-Loaded Shark MHC Class I Molecule Reveals Features of the Binding between β2-Microglobulin and H Chain Conserved in Evolution
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Autor/in / Beteiligte Person: | Li, Shen ; Wu, Yanan ; Xia, Chun ; Zhang, Nianzhi ; Hashimoto, Keiichiro ; Dijkstra, Johannes M. ; Wei, Xiaohui ; Lu, Shuangshuang |
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Zeitschrift: | The Journal of Immunology, Jg. 207 (2021-07-01), S. 308-321 |
Veröffentlichung: | The American Association of Immunologists, 2021 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.2001165 |
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