Membrane curvature recognition by C-reactive protein using lipoprotein mimics.

Membrane curvature recognition by C-reactive protein using lipoprotein mimics.
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DOI:
10.1039/c2sm25779c
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发表时间:
2012-08-14
期刊:
影响因子:
3.4
通讯作者:
Reed SM
Reed SM
中科院分区:
化学2区
文献类型:
--
作者:
Wang MS;Messersmith RE;Reed SM

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据报道,磷脂酰胆碱(PC)的氧化是C-反应蛋白(CRP)与脂质膜结合所必需的,但CRP为什么只与氧化膜结合仍不清楚。在这里,我们提供了一个新的视角膜曲率和CRP结合的作用,使用工程脂蛋白颗粒(LPP)模拟。我们发现CRP优先结合直径≤ 28 nm的LPP模拟物,CRP与这些模拟物的结合导致天然CRP解离为单体CRP,暴露出结合C1 q的CRP新表位。我们还表明,较小的LPP模拟竞争CRP结合氧化低密度脂蛋白(oxLDL),这表明这些模拟暴露相同的PC表位上发现的oxLDL。这项研究的结果表明,膜曲率可能是一个额外的因素,影响CRP结合受损膜不同的PC脂质的氧化。
It has been reported that the oxidation of phosphatidylcholine (PC) is necessary for C-reactive protein (CRP) to bind to lipid membranes, but it remains elusive why CRP only binds oxidized membranes. Here we offer a new perspective on the role of membrane curvature and CRP binding using engineered lipoprotein particle (LPP) mimics. We show that CRP binds preferentially to LPP mimics with diameters of ≤ 28 nm, and binding of CRP to these mimics leads to the dissociation of native CRP into monomeric CRP, exposing CRP neo-epitopes that bind C1q. We also show that the smaller LPP mimics compete for CRP binding to oxidized low density lipoproteins (oxLDLs), suggesting that these mimics expose the same PC epitopes as those found on oxLDLs. Results from this study suggest that membrane curvature could be an additional factor influencing CRP binding of damaged membranes distinct from the oxidation of PC lipids.