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a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre-T cell receptors (preTCRs) and \u03b1\u03b2TCRs. Using x-ray crystallography, we show how a preTCR applies the concave \u03b2-sheet surface of its single variable domain (V\u03b2) to \"horizontally\" grab the protruding MHC \u03b12-helix. By contrast, \u03b1\u03b2TCRs purpose all six complementarity-determining region (CDR) loops of their paired V\u03b1V\u03b2 module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in \"vertical\" head-to-head binding. The preTCR topological fit ensures that CDR3\u03b2 reaches the peptide's featured C-terminal segment for pMHC sampling, establishing the subsequent \u03b1\u03b2TCR canonical docking mode. \"Horizontal\" docking precludes germline CDR1\u03b2- and CDR2\u03b2-MHC binding to broaden \u03b2-chain repertoire diversification before \u03b1\u03b2TCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors.","bibjson":{"author":[{"initials":"X","lastname":"Li","name":"Li X"},{"initials":"R","lastname":"Mizsei","name":"Mizsei R"},{"initials":"K","lastname":"Tan","name":"Tan K"},{"initials":"RJ","lastname":"Mallis","name":"Mallis RJ"},{"initials":"JS","lastname":"Duke-Cohan","name":"Duke-Cohan JS"},{"initials":"A","lastname":"Akitsu","name":"Akitsu A"},{"initials":"PW","lastname":"Tetteh","name":"Tetteh PW"},{"initials":"A","lastname":"Dubey","name":"Dubey A"},{"initials":"W","lastname":"Hwang","name":"Hwang W"},{"initials":"G","lastname":"Wagner","name":"Wagner G"},{"initials":"MJ","lastname":"Lang","name":"Lang MJ"},{"initials":"H","lastname":"Arthanari","name":"Arthanari H"},{"initials":"JH","lastname":"Wang","name":"Wang JH"},{"initials":"EL","lastname":"Reinherz","name":"Reinherz EL"}],"identifier":[{"id":"10.1126/science.abe0918","type":"doi"},{"id":"33335016","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Science","name":""},"pages":[null],"title":"Pre-T cell receptors topologically sample self-ligands during thymocyte \ufffd\ufffd-selection.","type":"article","url":"https://www.science.org/doi/10.1126/science.abe0918","volume":[null],"year":[2020]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"3.45","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6wl3"},"rcsb":{"url":"https://www.rcsb.org/structure/6wl3"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":null,"title":"Truncated H2-Kb binding \"RGYLYQGL\" with pre TCR beta chain at 3.45&#8491; resolution","unique_chain_count":3}}
