NTB-A receptor crystal structure: insights into homophilic interactions in the signaling lymphocytic activation molecule receptor family.
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.
Cao
Erhu
E
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Ramagopal
Udupi A
UA
Fedorov
Alexander
A
Fedorov
Elena
E
Yan
Qingrong
Q
Lary
Jeffrey W
JW
Cole
James L
JL
Nathenson
Stanley G
SG
Almo
Steven C
SC
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
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