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
| Autor: | Shen Li, Yanan Wu, Chun Xia, Nianzhi Zhang, Keiichiro Hashimoto, Johannes M. Dijkstra, Xiaohui Wei, Shuangshuang Lu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Alanine biology Hydrogen bond Stereochemistry Beta-2 microglobulin Immunology chemical and pharmacologic phenomena Peptide Major histocompatibility complex biology.organism_classification 03 medical and health sciences 0302 clinical medicine chemistry MHC class I biology.protein Immunology and Allergy Proline Nurse shark 030215 immunology |
| Zdroj: | The Journal of Immunology. 207:308-321 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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