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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, \u03b2<sub>2</sub>-microglobulin (\u03b2<sub>2</sub>-m), and peptide ligand. In most previous studies, relatively little attention was given to the details of binding between the H chain and \u03b2<sub>2</sub>-m, and our study provides important new insights. A pronounced conserved feature involves the insertion of a large \u03b2<sub>2</sub>-m F56+W60 hydrophobic knob into a pleat of the \u03b2-sheet floor of the H chain \u03b11\u03b12 domain, with the knob being surrounded by conserved residues. Another conserved feature is a hydrogen bond between \u03b2<sub>2</sub>-m Y10 and a proline in the \u03b13 domain of the H chain. By alanine substitution analysis, we found that the conserved \u03b2<sub>2</sub>-m residues Y10, D53, F56, and W60-each binding the H chain-are required for stable pMHC-I complex formation. For the \u03b2<sub>2</sub>-m residues Y10 and F56, such observations have not been reported before. The combined data indicate that for stable pMHC-I complex formation \u03b2<sub>2</sub>-m should not only bind the \u03b11\u03b12 domain but also the \u03b13 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.","bibjson":{"author":[{"initials":"Y","lastname":"Wu","name":"Wu Y"},{"initials":"N","lastname":"Zhang","name":"Zhang N"},{"initials":"X","lastname":"Wei","name":"Wei X"},{"initials":"S","lastname":"Lu","name":"Lu S"},{"initials":"S","lastname":"Li","name":"Li S"},{"initials":"K","lastname":"Hashimoto","name":"Hashimoto K"},{"initials":"JM","lastname":"Dijkstra","name":"Dijkstra JM"},{"initials":"C","lastname":"Xia","name":"Xia C"}],"identifier":[{"id":"10.4049/jimmunol.2001165","type":"doi"},{"id":"34145057","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"J Immunol","name":""},"pages":[null],"title":"The Structure of a Peptide-Loaded Shark MHC Class I Molecule Reveals Features of the Binding between \ufffd\ufffd<sub>2</sub>-Microglobulin and H Chain Conserved in Evolution.","type":"article","url":"http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.2001165","volume":[null],"year":[2021]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"2.30","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6lup"},"rcsb":{"url":"https://www.rcsb.org/structure/6lup"}},"species":{"common_name":"Nurse shark","match_type":"histo:assign_species","scientific_name":"Ginglymostoma cirratum","slug":"ginglymostoma_cirratum"},"tcr":null,"title":"Gici-UAA01 binding \"FANFFIRGL\" at 2.30&#8491; resolution","unique_chain_count":3}}
