INSERM UMRS 937, Génomique Cardiovasculaire, Paris, France.
J Leukoc Biol. 2010 Apr;87(4):727-34. doi: 10.1189/jlb.0609408. Epub 2010 Jan 5.
Interactions between P-sel and the PSGL-1 mediate the earliest adhesive events during an inflammatory response. Human PSGL-1 displays a high degree of genetic polymorphism that has been diversely associated with susceptibility to human diseases. In the central part of PSGL-1, a 10-aa motif is repeated 14, 15, or 16 times. Moreover, two mutations, M62I and M274V, are often found giving the most common variant M62-M274 with 16 motifs (M16M) and its variants I62-M274 (I16M). Two other variants exist with 15 repeated motifs (M62-M274; M15M) and with 14 motifs (M62-V274; M14V). We investigated the potential difference in the adhesive properties between these natural variants stably expressed in the HEK cell line by using the BFP technique. Their interactions with P-sel were found to be of catch bond-type, and the dissociation force was primarily dependent on the number of decameric motifs: the shorter the PSGL-1, the larger the bond strength. Finally, we found that the M62I mutation, which is close to the binding site to P-sel, reduced the adhesiveness to P-sel effectively. Collectively, these data shed new light on the polymorphism of PSGL-1 and could help the research on its associations to human pathologies.
P-选择素与 PSGL-1 之间的相互作用介导了炎症反应中最早的黏附事件。人类 PSGL-1 显示出高度的遗传多态性，与人类疾病的易感性有很大的关联。在 PSGL-1 的中心部分，有一个 10 个氨基酸的基序重复了 14、15 或 16 次。此外，经常发现两个突变 M62I 和 M274V，它们赋予最常见的变体 M62-M274 16 个基序（M16M）及其变体 I62-M274（I16M）。另外两种变体存在 15 个重复的基序（M62-M274；M15M）和 14 个基序（M62-V274；M14V）。我们通过使用 BFP 技术，研究了这些在 HEK 细胞系中稳定表达的天然变体在黏附特性上的潜在差异。发现它们与 P-选择素的相互作用属于捕获键型，解离力主要取决于十聚体基序的数量：PSGL-1 越短，键强度越大。最后，我们发现靠近与 P-选择素结合位点的 M62I 突变有效地降低了与 P-选择素的黏附性。总之，这些数据为 PSGL-1 的多态性提供了新的见解，并有助于研究其与人类病理学的关联。
