The platelet integrin alphaIIbbeta3 binds to the RGD and AGD motifs in fibrinogen.
The platelet integrin alphaIIbbeta3 binds to the RGD and AGD motifs in fibrinogen.
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DOI：
10.1016/j.chembiol.2009.08.012
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发表时间：
2009-09-25
影响因子：
--
通讯作者：
Mrksich M
中科院分区：
文献类型：
--
作者：
Sánchez-Cortés J;Mrksich M
纤维蛋白原（Fbg）通过与αIIbβ3整联蛋白受体结合介导血小板聚集。尽管有许多关于血小板聚集和凝血的研究，但Fbg与血小板整合素的相互作用仍然没有得到解决。本文报道了使用烷基硫醇盐在金表面的自组装单分子膜（SAMs）研究αIIbβ3 CHO K1细胞与Fbg内GRGDS和HHLGGAKQAGDV基序的粘附。将肽固定到单层上，以防止细胞与底物的非特异性相互作用。呈现GRGDSC或HHLGGAKQAGDVC的单层在介导αIIbβ3 CHO K1细胞粘附和铺展方面有效，并且与使用Fbg包被基质相当，表明两种序列均可独立结合受体。细胞粘附几个肽截短的比较显示，AGD是HHLGGAKQAGDV的最小结合序列，抑制实验表明，AGD和RGD的受体的竞争性配体。GXGDSC肽的肽阵列显示，αIIbβ3 CHO K1细胞粘附在X位置含有碱性或疏水残基的肽上，揭示了αIIbβ3识别其配体的松弛特异性。因此，这项工作表明，AGD和RGD以功能相似的方式与Fbg相互作用，并且AGD肽的使用可能导致新一代抗血栓形成剂。
Fibrinogen (Fbg) mediates platelet aggregation through its binding to the αIIbβ3 integrin receptor. Despite the many studies of platelet aggregation and blood clotting, the interaction of Fbg with the platelet integrin has remained unresolved. This paper reports on the use of self-assembled monolayers (SAMs) of alkanethiolates on gold to study the adhesion of αIIbβ3 CHO K1 cells to the GRGDS and HHLGGAKQAGDV motifs within Fbg. The peptides were immobilized to a monolayer that otherwise prevented nonspecific interactions of the cells with the substrate. Monolayers presenting GRGDSC or HHLGGAKQAGDVC were effective at mediating αIIbβ3 CHO K1 cell adhesion and spreading and were comparable to the use of Fbg-coated substrates, suggesting that both sequences can bind the receptor independently. A comparison of cell adhesion to several peptide truncations revealed that AGD was the minimal binding sequence in HHLGGAKQAGDV, and inhibition experiments showed that AGD and RGD were competitive ligands for the receptor. A peptide array of GXGDSC peptides revealed that αIIbβ3 CHO K1 cells adhered to peptides containing basic or hydrophobic residues in the X position, revealing the relaxed specificity with which αIIbβ3 recognizes its ligands. This work therefore suggests that AGD and RGD interact with Fbg in a functionally similar manner and that the use of AGD peptides may lead to a new generation of anti-thrombotic agents.
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