Localization and characterization of a heparin binding domain peptide of human von Willebrand factor.
Localization and characterization of a heparin binding domain peptide of human von Willebrand factor.
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DOI：
10.1016/s0021-9258(19)50359-3
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发表时间：
1992-05
期刊：
影响因子：
--
通讯作者：
M. Sobel;D. Soler;J. Kermode;R. Harris
中科院分区：
文献类型：
--
作者：
M. Sobel;D. Soler;J. Kermode;R. Harris
人血管性血友病因子是一种血浆糖蛋白，在调节止血中起关键作用，可与肝素结合，但这种相互作用的生理重要性和模式知之甚少。使用共有肝素结合合成肽的氨基酸序列的基序，鉴定了人血管性血友病因子的23个残基序列（Tyr 565-Ala 587），其保留了共有基序并且以与天然血管性血友病因子和共有肽相当的亲和力结合肝素。在液相结合试验中，Tyr 565-Ala 587肽与血管性血友病因子有效竞争结合肝素。合成和测试肽重叠Tyr 565-Ala 587，以及相邻的阳离子区域，显示该核心序列是最佳的线性结合结构域。Tyr 565-Ala 587肽的远紫外圆二色光谱表明，该肽在结合肝素时发生构象变化。Tyr 565-Ala 587肽因此包含部分（或全部）功能上重要的血管性血友病因子肝素结合结构域。进一步研究这种肽和相关肽可能有助于探索肝素如何影响血管性血友病因子介导的血小板止血。
Human von Willebrand factor, a plasma glycoprotein which plays a critical role in regulating hemostasis, binds heparin, but the physiological importance and mode of this interaction is poorly understood. Using the motif of an amino acid sequence of a consensus heparin binding synthetic peptide, a 23-residue sequence (Tyr565-Ala587) of human von Willebrand factor was identified that retains the consensus motif and binds heparin with affinity comparable with native von Willebrand factor and the consensus peptide. In a fluid phase binding assay, the Tyr565-Ala587 peptide competed effectively with von Willebrand factor for binding heparin. Synthesis and testing of peptides overlapping Tyr565-Ala587, as well as adjacent cationic regions, showed this core sequence to be the optimal linear binding domain. Far ultraviolet circular dichroism spectrometry of the Tyr565-Ala587 peptide suggested that the peptide undergoes conformational change upon binding heparin. The Tyr565-Ala587 peptide thus encompasses part (or all) of a functionally important heparin binding domain of von Willebrand factor. Further study of this and related peptides may be useful for exploring how heparin may influence von Willebrand factor-mediated platelet hemostasis.