ASSEMBLY OF HIGH-DENSITY LIPOPROTEINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 高密度脂蛋白（HDL）（http：//www.ks.uiuc.edu/Research/Lipoproteins/）是参与胆固醇从外周组织转运至肝脏进行降解的蛋白质-脂质组装体。HDL通常被称为 好胆固醇 由于其在从组织和血管中去除过量胆固醇中的作用。 低于平均水平的HDL与冠心病风险增加有关。 HDL的产生、转化和降解受胆固醇逆向转运途径的调节。载脂蛋白A-I（apo A-I）是HDL的主要蛋白组分，最初形成无脂质/贫HDL颗粒。 胆固醇和脂质掺入无脂质/贫HDL颗粒引起结构变化，形成盘状脂蛋白颗粒。 胆固醇和脂质的持续流出以及胆固醇的酯化导致盘状颗粒转化为成熟的球形颗粒，其将胆固醇转运到肝脏[1]。 已确定无脂质载脂蛋白A-I的两种X射线晶体结构[2，3];然而，与脂质结合的载脂蛋白A-I的结构（盘状或球形HDL形式）仍未知。由于天然HDL颗粒在尺寸和组成上是不均匀的，因此不可能获得关于它们的一致结构数据[4]。 然而，重构HDL（rHDL），其中纯化的（并且通常截短的）apo A-I用于形成HDL颗粒，可以制成均质颗粒。 纳米圆盘是一种工程rHDL模拟物，由资源合作者S。Sligar（UIUC），其可以使用一组精确的优化条件自组装以形成具有均匀尺寸和组成的盘状蛋白质-脂质颗粒[5]。该资源在我们的分子动力学研究中利用这些均匀且特征良好的纳米盘颗粒[6，7][8，9]。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. High-density lipoproteins (HDL) (http://www.ks.uiuc.edu/Research/Lipoproteins/) are protein-lipid assemblies involved in the transport of cholesterol from peripheral tissues to the liver for degradation. HDL is often called good cholesterol due to its role in removing excess cholesterol from tissues and blood vessels. Lower than average levels of HDL have been implicated in an increased risk of coronary heart disease. The production, transformation, and degradation of HDL is regulated by the reverse cholesterol transport pathway. Apolipoprotein A-I (apo A-I), the primary protein component of HDL, initially forms lipid-free/poor HDL particles. The incorporation of cholesterol and lipids into lipid-free/poor HDL particles causes a structural change, forming discoidal lipoprotein particles. Continued efflux of cholesterol and lipids as well as the esterification of cholesterol results in the transformation of the discoidal particles into mature spherical particles, which transport the cholesterol to the liver [1]. Two X-ray crystal structures of lipid-free apo A-I have been determined [2, 3]; however, the structure of apo A-I bound to lipid, in either the discoidal or spherical HDL forms, remains unknown. Since natural HDL particles are heterogeneous in size and composition, it has been impossible to obtain consistent structural data on them [4]. However, reconstituted HDL (rHDL), in which purified (and often truncated) apo A-I is used to form HDL particles, can be made into homogeneous particles. Nanodiscs are an engineered rHDL mimic being developed by Resource collaborator S. Sligar (UIUC), which can be self-assembled using a precise set of optimized conditions to form discoidal protein-lipid particles with homogeneous size and composition [5]. The Resource utilizes these homogeneous and well-characterized nanodisc particles [6, 7] in our molecular dynamics studies [8, 9].