CD36, A SCAVENGER RECEPTOR AND HDL, HIGH DENSITY LIPOPROTEIN

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 CD 36的晶体筛选。 CD 36是一种膜受体，被认为具有处理胆固醇和氧化脂质的功能。 然而，最近许多实验室的研究结果表明，CD 36参与动脉斑块的形成，这是导致心脏病发作的动脉粥样硬化的主要原因。 其全长蛋白由441个氨基酸组成，分子量约为50 K。 它的结构从未被确定。我们的项目的目标是找出CD 36与心脏病发作之间的相关性。 高密度脂蛋白的晶体筛选。 高密度脂蛋白是所谓的好胆固醇载体，其功能是将胆固醇从外周运送到肝脏进行催化。 我们研究的目的是找出这种转运过程的机制，医学上称为胆固醇逆向转运RCT）。由于HDL是RCT中的关键参与者，HDL的结构肯定会给我们更多的线索，寻找新的方法或药物来对抗动脉粥样硬化。 HDL的结构从未被确定到高分辨率。 存在基于生物物理、生物化学和计算方法的若干模型。 然而，它们更多的是间接的理论性质，而不是直接的实验结果。最近我们发表了一个基于中子散射和计算改进的低分辨率模型。 我们的模型与其他实验室提出的模型有着根本的不同。 一场新的辩论从此开始。为了找到一个高分辨率的实验模型，我们必须求助于基于颗粒的高分子量（超过200 kDa）的蛋白质晶体学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Crystal screening of CD36. CD36 is a membrane receptor supposedly with the function of disposing cholesterol and oxidized lipid. However, recent findings of many labs indicated that CD36 is involved in the formation of plaques in the arteries, the main cause of atherosclerosis which leads to hear attacks. It has 441 amino acids for the full length protein and the MW is around 50 K. Its structure has never been determined. The goal of our project is to find out the correlation between CD36 and heart attack. Crystal screening of HDL, the high density lipo-protein. HDL is the so-called good cholesterol carrier which functions as a vehicle to carry the cholesterol from the periphery to the liver for catabolism. The goal of our study is to find out the mechanism of this transport process medically called the reverse cholesterol transport RCT). Since HDL is a key player in RCT the structure of HDL will certainly give us more clue in finding new way or drugs to combat atherosclerosis. The structure of HDL has never been determined to a high resolution. There exist several models based on biophysical, biochemical and computational methods. However, they are more of indirect theoretical in nature than direct experimental findings. Recently we have published a low resolution model based on Neutron Scattering and computational refinement. Our model is fundamentally different from what the other labs suggested. A new debate has since been kindled. To find out a high resolution experimental model we have to resort to protein crystallography based on the high molecular weight of the particle (more than 200 kDa).