title: Distinct conformations of Ly49 natural killer cell receptors mediate MHC class I recognition in trans and cis.
abstract: Certain cell-surface receptors engage ligands expressed on juxtaposed cells and ligands on the same cell. The structural basis for trans versus cis binding is not known. Here, we showed that Ly49 natural killer (NK) cell receptors bound two MHC class I (MHC-I) molecules in trans when the two ligand-binding domains were backfolded onto the long stalk region. In contrast, dissociation of the ligand-binding domains from the stalk and their reorientation relative to the NK cell membrane allowed monovalent binding of MHC-I in cis. The distinct conformations (backfolded and extended) define the structural basis for cis-trans binding by Ly49 receptors and explain the divergent functional consequences of cis versus trans interactions. Further analyses identified specific stalk segments that were not required for MHC-I binding in trans but were essential for inhibitory receptor function. These data identify multiple distinct roles of stalk regions for receptor function.
authors.affiliation: Ludwig Institute for Cancer Research Ltd., Lausanne Branch and University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Back
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Malchiodi
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Cho
authors.forename: Léonardo
authors.initials: L
authors.lastname: Scarpellino
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Kerzic
authors.forename: Roy A
authors.initials: RA
authors.lastname: Mariuzza
authors.forename: Werner
authors.initials: W
authors.lastname: Held
mesh_terms: D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A