CRYSTAL STRUCTURE OF THE NATURAL KILLER CELL RECEPTOR 2B4 IN COMPLEX WITH CD48

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。作为先天免疫的一部分，自然杀伤（NK）细胞能够杀死某些肿瘤和病毒感染的细胞。细胞表面上的活化性和抑制性受体之间的精细平衡控制NK细胞的细胞溶解活性。抑制性受体通过识别健康宿主细胞上的I类MHC分子提供免于裂解的保护。活化NK受体通过特异性配体识别介导肿瘤或病毒感染细胞的杀伤。与抑制性受体相反，对激活性NK受体的结构知之甚少。2B 4是一种主要在NK细胞和CD 8 + T细胞亚群上表达的跨膜受体，通过与靶细胞上的CD 48相互作用，在激活NK介导的细胞毒性中发挥重要作用。2B 4包含两个Ig样细胞外结构域（D1和D2）和一个含有CxC/+基序的细胞质部分，该基序可结合接头中的互补CxxC/基序以激活T细胞（LAT）。除LAT外，2B 4的胞质尾区结合含SH 2结构域的蛋白SAP。这种关联对于2B 4向NK细胞传递激活信号至关重要。事实上，在不存在SAP的情况下，2B 4转导导致NK细胞失活的抑制信号。发现2B 4可以激活和抑制NK细胞溶解，结合鉴定CD 48作为其生物配体，使2B 4成为结构分析的引人注目的靶标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As part of innate immunity, natural killer (NK) cells are capable of killing certain tumor and virally infected cells. A fine balance between the activating and inhibitory receptors on the cells surface controls the cytolytic activity of NK cells. The inhibitory receptors provide the protection from lysis by recognizing class I MHC molecules on healthy host cells. Activating NK receptors mediate the killing of tumor or virally infected cells through specific ligand recognition. In contrast to the inhibitory receptors, much less is known about the structures of activating NK receptors. 2B4, a transmembrane receptor expressed primarily on NK cells and on a subset of CD8+ T cells, plays an important role in activating NK-mediated cytotoxicity through its interaction with CD48 on target cells. 2B4 comprises two Ig-like extracellular domains (D1 and D2) and a cytoplasmic portion containing a CxC/+ motif that may bind a complementary CxxC/¿¿¿ motif in the linker for activation of T cells (LAT). In addition to LAT, the cytoplasmic tail of 2B4 binds the SH2 domain-containing protein SAP. This association is crucial for 2B4 to deliver activating signals to NK cells. Indeed, in the absence of SAP, 2B4 tranduces inhibitory signals that result in NK cell inactivation. The finding that 2B4 can both activate and inhibit NK cytolysis, combined with the identification of CD48 as its biological ligand, make 2B4 a compelling target for structural analysis.