“von Willebrand因子”與血小板表面上“糖蛋白Ib a”的結(jié)合調(diào)控血小板的交聯(lián)，是血液凝固中的一個重要因素,。利用將一個受體與其配體在單個分子中聯(lián)系起來以測定結(jié)合和斷開過程的一種新方法,，Kim等人識別出一個以前沒有被識別處的鍵行為類型。“受體-配體”鍵存在于兩種截然不同的狀態(tài)：一種是所謂的“輕力”(low force)狀態(tài),，另一種是更為穩(wěn)定的狀態(tài)——該狀態(tài)是當(dāng)施加張力時出現(xiàn)的,，使該鍵相對于所施加的力保持穩(wěn)定。
這種“柔性鍵”行為——它涉及兩組“滑動鍵”（鍵壽命隨負載增加而縮短）而不是“逆鎖鍵”（鍵壽命隨所施加的力增加）之間的切換——的發(fā)現(xiàn),，對于了解與“von Willebrand因子”結(jié)合在一起的血小板何以能夠抵抗外力,、對于血流的增加何以會激發(fā)血小板栓子的形成都有意義。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature doi:10.1038/nature09295
A mechanically stabilized receptor–ligand flex-bond important in the vasculature
Jongseong Kim,Cheng-Zhong Zhang,Xiaohui Zhang& Timothy A. Springer
Haemostasis in the arteriolar circulation mediated by von Willebrand factor (VWF) binding to platelets is an example of an adhesive interaction that must withstand strong hydrodynamic forces acting on cells. VWF is a concatenated, multifunctional protein that has binding sites for platelets as well as subendothelial collagen1, 2. Binding of the A1 domain in VWF to the glycoprotein Ib α subunit (GPIbα) on the surface of platelets mediates crosslinking of platelets to one another and the formation of a platelet plug for arterioles3, 4. The importance of VWF is illustrated by its mutation in von Willebrand disease, a bleeding diathesis1. Here, we describe a novel mechanochemical specialization of the A1–GPIbα bond for force-resistance. We have developed a method that enables, for the first time, repeated measurements of the binding and unbinding of a receptor and ligand in a single molecule (ReaLiSM). We demonstrate two states of the receptor–ligand bond, that is, a flex-bond. One state is seen at low force; a second state begins to engage at 10?pN with a ~20-fold longer lifetime and greater force resistance. The lifetimes of the two states, how force exponentiates lifetime, and the kinetics of switching between the two states are all measured. For the first time, single-molecule measurements on this system are in agreement with bulk phase measurements. The results have important implications not only for how platelets bound to VWF are able to resist force to plug arterioles, but also how increased flow activates platelet plug formation.
