Rye K A, Hime N J, Barter P J
Division of Cardiovascular Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia 5000.
J Biol Chem. 1997 Feb 14;272(7):3953-60. doi: 10.1074/jbc.272.7.3953.
It is well established that cholesteryl ester transfer protein (CETP) changes the size of high density lipoproteins (HDL) during incubation in vitro. It has been suggested that HDL.CETP.HDL ternary complex formation is involved in these changes. The present results, which are consistent with CETP changing the size of spherical reconstituted HDL (rHDL) by a mechanism involving fusion, support the ternary complex hypothesis. When rHDL containing a core of cholesteryl esters and either three molecules of apolipoprotein (apo) A-I/particle, (A-I)rHDL, or six molecules of apoA-II/particle, (A-II)rHDL, were incubated individually with CETP, their respective diameters decreased from 9.4 to 7.8 nm and from 9.8 to 8.8 nm. The small (A-I)rHDL and (A-II)rHDL contained, respectively, two molecules of apoA-I/particle and four molecules of apoA-II/particle. As all of the rHDL lipids and apolipoproteins were quantitatively recovered at the end of the incubations, it was apparent that there was a 50% increase in the number of particles. This increase in the number of particles can be explained as follows: (i) sequential binding of two rHDL to CETP to generate a ternary complex, (ii) fusion of the rHDL in the ternary complex, and (iii) rearrangement of the fusion product into three small particles. Various spectroscopic techniques were used to show that the small rHDL were structurally distinct from the original rHDL. These results provide the first evidence that CETP mediates the fusion of spherical rHDL.
众所周知，胆固醇酯转运蛋白（CETP）在体外孵育过程中会改变高密度脂蛋白（HDL）的大小。有人提出，HDL - CETP - HDL三元复合物的形成与这些变化有关。目前的结果与CETP通过涉及融合的机制改变球形重组HDL（rHDL）大小一致，支持了三元复合物假说。当含有胆固醇酯核心且每颗粒分别含有三分子载脂蛋白（apo）A - I的rHDL，即（A - I）rHDL，或每颗粒含有六分子apoA - II的rHDL，即（A - II）rHDL，分别与CETP孵育时，它们各自的直径从9.4 nm降至7.8 nm，从9.8 nm降至8.8 nm。小的（A - I）rHDL和（A - II）rHDL分别每颗粒含有两分子apoA - I和四分子apoA - II。由于在孵育结束时所有的rHDL脂质和载脂蛋白都被定量回收，很明显颗粒数量增加了50%。颗粒数量的增加可以如下解释：（i）两个rHDL与CETP顺序结合以生成三元复合物，（ii）三元复合物中rHDL的融合，以及（iii）融合产物重排为三个小颗粒。使用了各种光谱技术来表明小rHDL在结构上与原始rHDL不同。这些结果提供了第一个证据，证明CETP介导球形rHDL的融合。
