Sanford Burnham Prebys Medical Discovery Institute, Degenerative Diseases Program, La Jolla, CA 92037, USA.
Trends Pharmacol Sci. 2018 Nov;39(11):953-966. doi: 10.1016/j.tips.2018.08.006.
Lysophospholipids (LPLs), particularly sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), are bioactive lipid modulators of cellular homeostasis and pathology. The discovery and characterization of five S1P- and six LPA-specific G protein-coupled receptors (GPCRs), S1P and LPA, have expanded their known involvement in all mammalian physiological systems. Resolution of the S1P, LPA, and LPA crystal structures has fueled the growing interest in these receptors and their ligands as targets for pharmacological manipulation. In this review, we have attempted to provide an integrated overview of the three crystallized LPL GPCRs with biochemical and physiological structure-function data. Finally, we provide a novel discussion of how chaperones for LPLs may be considered when extrapolating crystallographic and computational data toward understanding actual biological interactions and phenotypes.
溶血磷脂（LPLs），特别是鞘氨醇 1-磷酸（S1P）和溶血磷脂酸（LPA），是细胞内稳态和病理学的生物活性脂质调节剂。五种 S1P 和六种 LPA 特异性 G 蛋白偶联受体（GPCRs），S1P 和 LPA 的发现和表征，扩展了它们在所有哺乳动物生理系统中的已知参与。S1P、LPA 和 LPA 晶体结构的解析激发了人们对这些受体及其配体作为药理学操作靶点的浓厚兴趣。在这篇综述中，我们试图提供一个综合的概述与生物化学和生理学结构功能数据的三种结晶 LPL GPCR。最后，我们提供了一个新的讨论，即在将晶体学和计算数据外推到理解实际的生物学相互作用和表型时，如何考虑 LPL 的伴侣蛋白。
