Serum opacity factor unmasks human plasma high-density lipoprotein instability via selective delipidation and apolipoprotein A-I desorption
Serum opacity factor unmasks human plasma high-density lipoprotein instability via selective delipidation and apolipoprotein A-I desorption
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DOI：
10.1021/bi701525w
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发表时间：
2007-11-13
期刊：
影响因子：
2.9
通讯作者：
Pownall, Henry J.
中科院分区：
文献类型：
--
作者：
Gillard, Baiba K.;Courtney, Harry S.;Pownall, Henry J.
人血浆高密度脂蛋白（HDL）是胆固醇逆向转运的重要载体，胆固醇逆向转运是外周组织胆固醇转运到肝脏进行处置的心脏保护机制。HDL是血清混浊因子（SOF）的目标，SOF是一种由化脓性链球菌产生的物质，可使哺乳动物血清变浑浊。利用重组（r）SOF，我们研究了乳浊及其机制。rSOF催化HDL部分转化为富含胆固醇酯的微乳液（CERM）和新的HDL样颗粒neo HDL，同时释放无脂质（LF）-apo A-I。不透明是独一无二的; rSOF将apoE和几乎所有类似于100，000 HDL颗粒的中性脂质转移到单个大CERM中，其尺寸随HDL-CE含量增加而增加（r类似于100-250 nm），留下富含PL（41%）和蛋白质（48%）的neo HDL，特别是apoA-II。rSOF是有效的;在37 ℃下30分钟内，10 nM rSOF使4 μ M HDL不透明。在相应的低和高生理HDL浓度下，LF-apo A-I是单体和四聚体。CERM形成和apo A-I释放具有相似的动力学，表明平行或快速顺序步骤。根据反应产物和动力学。rSOF是一种异源二价融合蛋白，其使用对接位点置换载脂蛋白A-I并结合HDL上暴露的CE表面;所得的rSOF-HDL复合物通过其结合-脱脂位点募集额外的HDL，并通过多个融合步骤形成CERM。rSOF可能是一种临床上有用的和新的模式，用于改善胆固醇的反向转运。在载脂蛋白E和高CE含量的情况下，CERM可以将大量胆固醇转移到肝脏，通过LDL受体进行处理;新HDL可能是比HDL更好的细胞胆固醇受体; LF-apo A-I可以通过ATP结合盒转运蛋白ABCA 1增强流出。
Human plasma high-density lipoproteins (HDL) are important vehicles in reverse cholesterol transport, the cardioprotective mechanism by which peripheral tissue-cholesterol is transported to the liver for disposal. HDL is the target of serum opacity factor (SOF), a substance produced by Streptococcus pyogenes that turns mammalian serum cloudy. Using a recombinant (r) SOF, we studied opacification and its mechanism. rSOF catalyzes the partial disproportionation of HDL into a cholesteryl ester-rich microemulsion (CERM) and a new HDL-like particle, neo HDL, with the concomitant release of lipid-free (LF)-apo A-I. Opacification is unique; rSOF transfers apo E and nearly all neutral lipids of similar to 100, -000 HDL particles into a single large CERM whose size increases with HDL-CE content (r similar to 100-250 nm) leaving a neo HDL that is enriched in PL (41%) and protein (48%), especially apo A-II. rSOF is potent; within 30 min at 37 degrees C, 10 nM rSOF opacifies 4 mu M HDL. At respective low and high physiological HDL concentrations, LF-apo A-I is monomeric and tetrameric. CERM formation and apo A-I release have similar kinetics suggesting parallel or rapid sequential steps. According to the reaction products and kinetics. rSOF is a heterodivalent fusogenic protein that uses a docking site to displace apo A-I and bind to exposed CE surfaces on HDL; the resulting rSOF-HDL complex recruits additional HDL with its binding-delipidation site and through multiple fusion steps forms a CERM. rSOF may be a clinically useful and novel modality for improving reverse cholesterol transport. With apo E and a high CE content, CERM could transfer large amounts of cholesterol to the liver for disposal via the LDL receptor; neo HDL is likely a better acceptor of cellular cholesterol than HDL; LF-apo A-I could enhance efflux via the ATP-binding casette transporter ABCA1.