Stahelin Robert V
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, Raclin-Carmichael Hall, 1234 Notre Dame Avenue, South Bend, IN 46617, USA.
J Lipid Res. 2009 Apr;50 Suppl(Suppl):S299-304. doi: 10.1194/jlr.R800078-JLR200. Epub 2008 Nov 13.
The spatial and temporal regulation of lipid molecules in cell membranes is a hallmark of cellular signaling and membrane trafficking events. Lipid-mediated targeting provides for strict control and versatility, because cell membranes harbor a large number of lipid molecules with variation in head group and acyl chain structures. Signaling and trafficking proteins contain a large number of modular domains that exhibit specific lipid binding properties and play a critical role in their localization and function. Nearly 20 years of research including structural, computational, biochemical and biophysical studies have demonstrated how these lipid-binding domains recognize their target lipid and achieve subcellular localization. The integration of this individual lipid-binding domain data in the context of the full-length proteins, macromolecular signaling complexes, and the lipidome is only beginning to be unraveled and represents a target of therapeutic development. This review brings together recent findings and classical concepts to concisely summarize the lipid-binding domain field while illustrating where the field is headed and how the gaps may be filled in with new technologies.
细胞膜中脂质分子的时空调节是细胞信号传导和膜运输事件的一个标志。脂质介导的靶向作用实现了严格的控制和多功能性，因为细胞膜含有大量头部基团和酰基链结构各异的脂质分子。信号传导和运输蛋白包含大量模块化结构域，这些结构域具有特定的脂质结合特性，并在其定位和功能中发挥关键作用。近20年的研究，包括结构、计算、生化和生物物理研究，已经证明了这些脂质结合结构域如何识别其靶脂质并实现亚细胞定位。将这些单个脂质结合结构域数据整合到全长蛋白质、大分子信号复合物和脂质组的背景下才刚刚开始被揭示，并且是治疗开发的一个目标。这篇综述汇集了最近的研究发现和经典概念，以简要总结脂质结合结构域领域，同时说明该领域的发展方向以及如何用新技术填补空白。
