Modulation of α-thrombin function by distinct interactions with platelet glycoprotein Ib-α
Modulation of α-thrombin function by distinct interactions with platelet glycoprotein Ib-α
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DOI：
10.1126/science.1084183
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发表时间：
2003-07-11
期刊：
影响因子：
56.9
通讯作者：
Ruggeri, ZM
中科院分区：
文献类型：
--
作者：
Celikel, R;McClintock, RA;Ruggeri, ZM
与血小板结合的凝血酶有助于止血，在病理条件下，可能导致血管血栓形成。我们已经确定了血小板糖蛋白Ibalpha（GpIbalpha）的结构结合凝血酶在2.3埃的分辨率和定义两个网站在GpIbalpha结合到两个不同的α-凝血酶分子的外位点II和外位点I，分别。GpIalpha占据可能是顺序的，因为与α-凝血酶外位点I结合的位点在未被占据的受体中似乎是隐蔽的，但当第一个凝血酶分子通过外位点II结合时暴露。这些相互作用可能通过介导GpIbalpha聚集和蛋白酶激活受体的裂解来调节α-凝血酶功能，从而促进血小板活化，同时通过阻断外位点I来限制纤维蛋白原凝血。
Thrombin bound to platelets contributes to stop bleeding and, in pathological conditions, may cause vascular thrombosis. We have determined the structure of platelet glycoprotein Ibalpha (GpIbalpha) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIbalpha that bind to exosite II and exosite I of two distinct alpha-thrombin molecules, respectively. GpIbalpha occupancy may be sequential, as the site binding to alpha-thrombin exosite I appears to be cryptic in the unoccupied receptor but exposed when a first thrombin molecule is bound through exosite II. These interactions may modulate alpha-thrombin function by mediating GpIbalpha clustering and cleavage of protease-activated receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I.