title: NTB-A receptor crystal structure: insights into homophilic interactions in the signaling lymphocytic activation molecule receptor family.
abstract: The signaling lymphocytic activation molecule (SLAM) family includes homophilic and heterophilic receptors that regulate both innate and adaptive immunity. The ectodomains of most SLAM family members are composed of an N-terminal IgV domain and a C-terminal IgC2 domain. NK-T-B-antigen (NTB-A) is a homophilic receptor that stimulates cytotoxicity in natural killer (NK) cells, regulates bactericidal activities in neutrophils, and potentiates T helper 2 (Th2) responses. The 3.0 A crystal structure of the complete NTB-A ectodomain revealed a rod-like monomer that self-associates to form a highly kinked dimer spanning an end-to-end distance of approximately 100 A. The NTB-A homophilic and CD2-CD58 heterophilic dimers show overall structural similarities but differ in detailed organization and physicochemical properties of their respective interfaces. The NTB-A structure suggests a mechanism responsible for binding specificity within the SLAM family and imposes physical constraints relevant to the colocalization of SLAM-family proteins with other signaling molecules in the immunological synapse.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Erhu
authors.initials: E
authors.lastname: Cao
authors.forename: Udupi A
authors.initials: UA
authors.lastname: Ramagopal
authors.forename: Alexander
authors.initials: A
authors.lastname: Fedorov
authors.forename: Elena
authors.initials: E
authors.lastname: Fedorov
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Yan
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Lary
authors.forename: James L
authors.initials: JL
authors.lastname: Cole
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000276:immunology; D018801:CD2 Antigens / Q000737:chemistry; D018968:CD58 Antigens / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000276:immunology; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D018801:CD2 Antigens; D018968:CD58 Antigens; D011956:Receptors, Cell Surface; C000604060:SLAMF6 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1