Hatters Danny M, Budamagunta Madhu S, Voss John C, Weisgraber Karl H
Gladstone Institutes of Cardiovascular and Neurological Diseases, San Francisco, California 94158, USA.
J Biol Chem. 2005 Oct 7;280(40):34288-95. doi: 10.1074/jbc.M506044200. Epub 2005 Aug 1.
Interaction of the amino- and carboxyl-terminal domains in apolipoprotein (apo) E, referred to as domain interaction, is predicted to be more pronounced in apoE4 than in apoE3 and to underlie the association of apoE4 with Alzheimer and cardiovascular diseases. However, direct physical proof for the domain interaction concept is lacking. To address this issue, fluorescence resonance energy transfer and electron paramagnetic resonance spectroscopy were used to probe the spatial proximity of the two domains of apoE. Both methods demonstrated that the two domains are closer in both lipid-free and phospholipid-bound apoE4 than in apoE3 as a result of domain interaction. In addition, as shown by electron paramagnetic resonance, the domains of apoE4 move apart to resemble more closely the distance in apoE3 when the isoforms are bound to triglyceride-rich emulsion particles. These results demonstrate that domain interaction is a structural property of apoE4 and that apoE adopts different conformations when complexed to different lipids.
载脂蛋白（apo）E中氨基末端和羧基末端结构域的相互作用，即结构域相互作用，预计在apoE4中比在apoE3中更为显著，并且是apoE4与阿尔茨海默病和心血管疾病关联的基础。然而，缺乏结构域相互作用概念的直接物理证据。为了解决这个问题，采用荧光共振能量转移和电子顺磁共振光谱来探测apoE两个结构域的空间接近度。两种方法均表明，由于结构域相互作用，在无脂质和结合磷脂的apoE4中，这两个结构域比在apoE3中更接近。此外，如电子顺磁共振所示，当这些异构体与富含甘油三酯的乳剂颗粒结合时，apoE4的结构域会分开，其距离更接近apoE3中的距离。这些结果表明，结构域相互作用是apoE4的一种结构特性，并且当apoE与不同脂质复合时会采取不同的构象。
