Richer Sarah M, Stewart Nichole K, Webb Sarah A, Tomaszewski John W, Oakley Martha G
Department of Chemistry, Indiana University, 212 South Hawthorne Drive, Bloomington, Indiana 47405, USA.
ACS Chem Biol. 2009 Sep 18;4(9):733-9. doi: 10.1021/cb900121r.
Phosphoinositide (PI) lipids are essential regulators of a wide variety of cellular functions. We present here the preparation of a multivalent analogue of a phosphatidylinositol-4,5-bisphosphate (PIP(2)) micelle containing only the polar headgroup portion of this lipid. We show that this dendrimer binds to the cytoskeletal protein profilin with an affinity indistinguishable from that of PIP(2), despite the fact that profilin discriminates between PIP(2) and its monomeric hydrolysis product inositol-1,4,5-triphosphate (IP(3)) under physiological conditions. These data demonstrate that the diacylglycerol (DAG) moiety of PIP(2) is not required for high-affinity binding and suggest that profilin uses multivalency as a key means to distinguish between the intact lipid and IP(3). The class of soluble membrane analogues described here is likely to have broad applicability in the study of protein.PI interactions.
磷酸肌醇（PI）脂质是多种细胞功能的重要调节因子。我们在此展示了一种仅包含磷脂酰肌醇 - 4,5 - 二磷酸（PIP(2)）脂质极性头部基团部分的多价类似物胶束的制备方法。我们发现，尽管在生理条件下，原肌球蛋白能区分PIP(2)及其单体水解产物肌醇 - 1,4,5 - 三磷酸（IP(3)），但这种树枝状聚合物与细胞骨架蛋白原肌球蛋白的结合亲和力与PIP(2)无法区分。这些数据表明，PIP(2)的二酰基甘油（DAG）部分对于高亲和力结合并非必需，这表明原肌球蛋白利用多价性作为区分完整脂质和IP(3)的关键手段。这里描述的可溶性膜类似物类别可能在蛋白质 - PI相互作用的研究中具有广泛的适用性。
