Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLeX and PSGL-1
Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLeX and PSGL-1
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DOI：
10.1016/s0092-8674(00)00138-0
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发表时间：
2000-10-27
期刊：
影响因子：
64.5
通讯作者：
Camphausen, RT
中科院分区：
文献类型：
--
作者：
Somers, WS;Tang, J;Camphausen, RT
P-、E-和L-选择素构成细胞粘附受体家族，其介导白细胞在发炎内皮上的初始束缚和滚动，作为它们牢固附着和外渗到组织中的前奏。选择素与唾液酸刘易斯（X）（SLe（X））样聚糖弱结合，但与特异性糖蛋白反受体（包括PSGL-1）具有高亲和力。在这里，我们报告的晶体结构的人P-和E-选择素的结构，含有凝集素和EGF（LE）域与SLe（X）共复合。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的N-末端结构域共复合的晶体结构。这些结构揭示了E-和P-选择素如何结合SLe（X）的差异以及P-选择素和PSGL-1之间高亲和力相互作用的分子基础。
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 Lewis(X) (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.