Wilkins A L, Yang W, Yang J J
Department of Chemistry and Center for Drug Design, Georgia State University, Atlanta, GA 30303, USA. chejjy@panther. gsu.edu
Curr Protein Pept Sci. 2003 Oct;4(5):367-73. doi: 10.2174/1389203033487063.
CD2 (cluster of differentiation 2) is a cell adhesion molecule expressed on T cells and is recognized as a target for CD48 (rats) and CD58 (humans). Tremendous progress has been achieved in understanding the function of CD2, the mechanism of molecular recognition and protein folding, thus, leading towards the use of this protein as a scaffold for protein design. CD2 has been shown to set quantitative thresholds in T cell activation both in vivo and in vitro. Further, intracellular CD2 signaling pathways and networks are being discovered by the identification of several cytosolic tail binding proteins. In addition, a new method for directly measuring heterophilic adhesion has been developed. The functional "hot spot" for the adhesion surface of CD2 and CD58 has been dissected. Detailed NMR studies reveal that rat CD2 weakly self-associates to form a homodimeric structure in solution. Dynamic interaction of CD2 with the GYF and SH3 domains has been investigated. CD2 has been shown to form fibrils in the presence of 2,2,2-trifluoroethanol (TFE) and at low pH. Furthermore, kinetic studies have been completed to monitor the effect of surface hydrophobic residues and intramolecular bridges on the folding pathways of CD2. Our lab has de novo designed single calcium-binding sites into domain 1 of rat CD2 (CD2-D1) with strong metal selectivity. In addition, the EF-hand motifs have been grafted into CD2 to understand the site-specific calcium-binding affinity of calmodulin and calcium-dependent cell adhesion.
CD2（分化簇2）是一种在T细胞上表达的细胞黏附分子，被认为是CD48（大鼠）和CD58（人类）的靶点。在理解CD2的功能、分子识别机制和蛋白质折叠方面已经取得了巨大进展，因此，这使得该蛋白可作为蛋白质设计的支架。已证明CD2在体内和体外的T细胞激活中设定定量阈值。此外，通过鉴定几种胞质尾结合蛋白，正在发现细胞内CD2信号通路和网络。此外，还开发了一种直接测量异嗜性黏附的新方法。已剖析了CD2和CD58黏附表面的功能性“热点”。详细的核磁共振研究表明，大鼠CD2在溶液中微弱地自我缔合形成同二聚体结构。已研究了CD2与GYF和SH3结构域的动态相互作用。已证明CD2在2,2,2-三氟乙醇（TFE）存在下和低pH时形成纤维。此外，已完成动力学研究以监测表面疏水残基和分子内桥对CD2折叠途径的影响。我们实验室已在大鼠CD2的结构域1（CD2-D1）中从头设计了具有强金属选择性的单个钙结合位点。此外，已将EF手基序嫁接到CD2中，以了解钙调蛋白的位点特异性钙结合亲和力和钙依赖性细胞黏附。
