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cell lysis is regulated by natural killer (NK) cell receptors that recognize class I MHC molecules. Here we report the crystal structure of the human immunoglobulin-like NK cell receptor KIR2DL2 in complex with its class I ligand HLA-Cw3 and peptide. KIR binds in a nearly orthogonal orientation across the alpha1 and alpha2 helices of Cw3 and directly contacts positions 7 and 8 of the peptide. No significant conformational changes in KIR occur on complex formation. The receptor footprint on HLA overlaps with but is distinct from that of the T-cell receptor. Charge complementarity dominates the KIR/HLA interface and mutations that disrupt interface salt bridges substantially diminish binding. Most contacts in the complex are between KIR and conserved HLA-C residues, but a hydrogen bond between Lys 44 of KIR2DL2 and Asn 80 of Cw3 confers the allotype specificity. KIR contact requires position 8 of the peptide to be a residue smaller than valine. A second KIR/HLA interface produced an ordered receptor-ligand aggregation in the crystal which may resemble receptor clustering during immune synapse formation.","bibjson":{"author":[{"initials":"JC","lastname":"Boyington","name":"Boyington JC"},{"initials":"SA","lastname":"Motyka","name":"Motyka SA"},{"initials":"P","lastname":"Schuck","name":"Schuck P"},{"initials":"AG","lastname":"Brooks","name":"Brooks AG"},{"initials":"PD","lastname":"Sun","name":"Sun PD"}],"identifier":[{"id":"10.1038/35014520","type":"doi"},{"id":"10850706","type":"pubmed"}],"issue":["6786"],"journal":{"iso_abbreviation":"Nature","name":""},"pages":["537-43"],"title":"Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand.","type":"article","url":"http://www.nature.com/articles/35014520","volume":["405"],"year":[2000]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"3.00","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/1efx"},"rcsb":{"url":"https://www.rcsb.org/structure/1efx"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-C*03:04 binding \"GAVDPLLAL\" with KIR NK receptor at 3.00&#8491; resolution","unique_chain_count":4}}
