title: Homo-oligomerization of the activating natural killer cell receptor NKp30 ectodomain increases its binding affinity for cellular ligands.
abstract: The natural cytotoxicity receptors, comprised of three type I membrane proteins NKp30, NKp44, and NKp46, are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. Among these, NKp30 is a major receptor targeting virus-infected cells, malignantly transformed cells, and immature dendritic cells. To date, only few cellular ligands of NKp30 have been discovered, and the molecular details of ligand recognition by NKp30 are poorly understood. Within the current study, we found that the ectodomain of NKp30 forms functional homo-oligomers that mediate high affinity binding to its corresponding cellular ligand B7-H6. Notably, this homo-oligomerization is strongly promoted by the stalk domain of NKp30. Based on these data, we suggest that homo-oligomerization of NKp30 in the plasma membrane of NK cells, which might be favored by IL-2-dependent up-regulation of NKp30 expression, provides a way to improve recognition and lysis of target cells by NK cells.
authors.affiliation: From the NK Cell Biology, Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, D-60596 Frankfurt am Main, Germany and.
authors.forename: Julia
authors.initials: J
authors.lastname: Herrmann
authors.forename: Hannah
authors.initials: H
authors.lastname: Berberich
authors.forename: Jessica
authors.initials: J
authors.lastname: Hartmann
authors.forename: Steffen
authors.initials: S
authors.lastname: Beyer
authors.forename: Karen
authors.initials: K
authors.lastname: Davies
authors.forename: Joachim
authors.initials: J
authors.lastname: Koch
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D007694:Killer Cells, Natural / Q000378:metabolism*; D008024:Ligands; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D061987:Sf9 Cells
chemical_list: D060887:B7 Antigens; D008024:Ligands; C431710:NCR3 protein, human; C542363:NCR3LG1 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3
keywords: B7-H6; Cancer Biology; Innate Immunity; Insect Cells; Membrane Proteins; NCR3; Natural Killer (NK) Cell; Protein Secretion; Protein Self-assembly; Stalk Domain