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

Yanan Wu, Nianzhi Zhang, Xiaohui Wei, Shuangshuang Lu, Shen Li, Keiichiro Hashimoto, Johannes M. Dijkstra, Chun Xia

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)308-321
Number of pages14
JournalJournal of Immunology
Volume207
Issue number1
DOIs
Publication statusPublished - 01-07-2021

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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