Somers W S, Tang J, Shaw G D, Camphausen R T
Genetics Institute, Wyeth Research, Cambridge, Massachusetts 02140, USA.
Cell. 2000 Oct 27;103(3):467-79. doi: 10.1016/s0092-8674(00)00138-0.
P-, E- and L-selectin constitute a family of cell adhesion receptors that mediate the initial tethering and rolling of leukocytes on inflamed endothelium as a prelude to their firm attachment and extravasation into tissues. The selectins bind weakly to sialyl Lewisx (SLe(X))-like glycans, but with high-affinity to specific glycoprotein counterreceptors, including PSGL-1. Here, we report crystal structures of human P- and E-selectin constructs containing the lectin and EGF (LE) domains co-complexed with SLe(X). We also present the crystal structure of P-selectin LE co-complexed with the N-terminal domain of human PSGL-1 modified by both tyrosine sulfation and SLe(X). These structures reveal differences in how E- and P-selectin bind SLe(X) and the molecular basis of the high-affinity interaction between P-selectin and PSGL-1.
P-选择素、E-选择素和L-选择素构成了一个细胞粘附受体家族，它们介导白细胞在炎症内皮细胞上的初始 tethering 和滚动，这是它们牢固附着并渗入组织的前奏。选择素与唾液酸化路易斯x（SLe(X)）样聚糖结合较弱，但与包括PSGL-1在内的特定糖蛋白反受体具有高亲和力。在这里，我们报告了包含凝集素和EGF（LE）结构域的人P-选择素和E-选择素构建体与SLe(X)共复合的晶体结构。我们还展示了P-选择素LE与经酪氨酸硫酸化和SLe(X)修饰的人PSGL-1 N端结构域共复合的晶体结构。这些结构揭示了E-选择素和P-选择素结合SLe(X)方式的差异以及P-选择素与PSGL-1之间高亲和力相互作用的分子基础。
