脂质组成对人血清淀粉样蛋白 A 在重建高密度脂蛋白颗粒中的结构特性的影响。

Effects of lipid composition on the structural properties of human serum amyloid A in reconstituted high-density lipoprotein particles.

机构信息

Laboratory of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan; Radioisotope Research Laboratory, School of Pharmacy, Kitasato University, Shirokane, Minato-ku, Tokyo, 108-8641, Japan.

Laboratory of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan; Laboratory of Functional Molecular Chemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan.

出版信息

Chem Phys Lipids. 2019 Jul;221:8-14. doi: 10.1016/j.chemphyslip.2019.03.001. Epub 2019 Mar 2.

DOI:10.1016/j.chemphyslip.2019.03.001

PMID:30836067

Abstract

Serum amyloid A (SAA) is a member of exchangeable apolipoproteins that predominantly exists as a component of high-density lipoproteins (HDL). During inflammation, SAA displaces apolipoprotein A-I from HDL and becomes the major protein constituents of HDL. In addition, HDL lipid composition is altered in response to inflammation, which may induce the structural reorganization of SAA and affect its function. Therefore, the physiological roles of HDL can be influenced by changes in their protein and lipid compositions that are triggered by inflammatory diseases. Here, the effect of HDL lipid composition on the structural properties of SAA was examined. Uniformly sized reconstituted HDL (rHDL) was prepared and mainly composed of phosphatidylcholine with a single additional lipid species. Results showed that changes in lipid composition had no significant impact on the helical content of SAA and its thermodynamic stability. However, rHDL lipid composition affected other structural properties of SAA, such as its tryptophan microenvironment and kinetic stability, and thus influenced the susceptibility of SAA to enzymatic digestion. Therefore, changes in HDL lipid composition may affect the physiological function of SAA and the pathogenesis of SAA-related diseases.

摘要

血清淀粉样蛋白 A（SAA）是可交换载脂蛋白的成员，主要存在于高密度脂蛋白（HDL）中。在炎症过程中，SAA 从 HDL 中置换载脂蛋白 A-I，并成为 HDL 的主要蛋白质成分。此外，HDL 脂质组成在炎症反应中发生改变，这可能诱导 SAA 的结构重排并影响其功能。因此，HDL 的生理功能可能受到炎症性疾病引发的蛋白质和脂质组成变化的影响。在此，研究了 HDL 脂质组成对 SAA 结构特性的影响。均匀大小的重组 HDL（rHDL）被制备并主要由磷脂酰胆碱组成，带有单个额外的脂质种类。结果表明，脂质组成的变化对 SAA 的螺旋含量及其热力学稳定性没有显著影响。然而，rHDL 脂质组成影响 SAA 的其他结构特性，如色氨酸微环境和动力学稳定性，从而影响 SAA 对酶消化的敏感性。因此，HDL 脂质组成的变化可能影响 SAA 的生理功能和 SAA 相关疾病的发病机制。