Apolipoproteins are vital to lipid metabolism and cholesterol transport in the human body. Here we present a structural study of the lipid-bound particles formed by ApoE3 in a full-length and a truncated version. The particles are formed with, respectively, POPC and DMPC and investigated by small-angle X-ray scattering and negative stain electron microscopy. We find that lipid-bound ApoE3 particles are elliptical, disc-shaped particles composed of a central lipid bilayer encircled by two amphipathic ApoE3 proteins. We went on to investigate a truncated form of ApoE3 containing only residue 80 to 255 (ApoE3^80–255), which is the central helical repeat segment of ApoE3. The lipid-bound ApoE3^80–255 particles are found to have the same morphology as the particles with full-length ApoE3. However, they are larger, and form more heterogeneous discoidal structures with four proteins per particle. This behavior is in contrast to ApoA1 where the highly similar helical repeat domain determines the size and stoichiometry of the formed particles both in the case of full-length and truncated ApoA1. Our data hence points towards different mechanisms for lipid bilayer structural modulation by ApoA1 and ApoE3 due to different roles of the non-repeat segments.

载脂蛋白对人体脂质代谢和胆固醇的运输至关重要。在这里，我们对由ApoE3形成的全长和截短形式的脂质结合颗粒进行结构研究。颗粒分别由POPC和DMPC形成，并通过小角X射线散射和负染色电子显微镜检查。我们发现脂质结合的ApoE3颗粒是由两个两亲性ApoE3蛋白质包围的中央脂质双层构成的椭圆形，盘状颗粒。我们继续研究截短形式的ApoE3，其仅包含残基80至255（ApoE3 ^80–255），这是^ApoE3的中心螺旋重复片段。脂质结合的ApoE3 ^80–255发现具有与全长ApoE3的颗粒相同的形态。但是，它们更大，并形成每个粒子具有四个蛋白质的更异构的盘状结构。此行为与ApoA1相反，在全长和截短的ApoA1中，高度相似的螺旋重复域决定了所形成颗粒的大小和化学计量。因此，由于非重复片段的作用不同，我们的数据指出了ApoA1和ApoE3对脂质双层结构调节的不同机制。