6luo
Structure of nurse shark beta-2-microglobulin
Structural highlights
FunctionPublication Abstract from PubMedCartilaginous 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, beta2-microglobulin (beta2-m), and peptide ligand. In most previous studies, relatively little attention was given to the details of binding between the H chain and beta2-m, and our study provides important new insights. A pronounced conserved feature involves the insertion of a large beta2-m F56+W60 hydrophobic knob into a pleat of the beta-sheet floor of the H chain alpha1alpha2 domain, with the knob being surrounded by conserved residues. Another conserved feature is a hydrogen bond between beta2-m Y10 and a proline in the alpha3 domain of the H chain. By alanine substitution analysis, we found that the conserved beta2-m residues Y10, D53, F56, and W60-each binding the H chain-are required for stable pMHC-I complex formation. For the beta2-m residues Y10 and F56, such observations have not been reported before. The combined data indicate that for stable pMHC-I complex formation beta2-m should not only bind the alpha1alpha2 domain but also the alpha3 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. The Structure of a Peptide-Loaded Shark MHC Class I Molecule Reveals Features of the Binding between beta2-Microglobulin and H Chain Conserved in Evolution.,Wu Y, Zhang N, Wei X, Lu S, Li S, Hashimoto K, Dijkstra JM, Xia C J Immunol. 2021 Jun 18. pii: jimmunol.2001165. doi: 10.4049/jimmunol.2001165. PMID:34145057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
