Raussens V, Fisher C A, Goormaghtigh E, Ryan R O, Ruysschaert J M
Laboratoire de Chimie Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles CP 206/2, bd. du Triomphe, B-1050 Brussels, Belgium.
J Biol Chem. 1998 Oct 2;273(40):25825-30. doi: 10.1074/jbc.273.40.25825.
Lipid association is a prerequisite for receptor interactions of apolipoprotein E (apoE). Disc complexes of the N-terminal 22-kDa apoE3 receptor binding domain and dimyristoylphosphatidylcholine display full receptor binding activity. Studies have been performed to characterize conformational adaptations of the globular, lipid-free four-helix bundle structure that culminate in stable association of its amphipathic alpha-helices with a lipid surface. Helix-lipid interactions in bilayer disc complexes can conceivably adopt two orientations: parallel or perpendicular to the phospholipid acyl chains. Evidence based on infrared dichroism, geometrical arguments, and x-ray crystallography support the view that defined helical segments in the four-helix bundle realign upon lipid association, orienting perpendicular to the phospholipid fatty acyl chains, circumscribing the bilayer disc. Thus, it is likely that paired helical segments align in tandem, presenting a convex receptor-active surface.
脂质结合是载脂蛋白E（apoE）与受体相互作用的前提条件。N端22 kDa的apoE3受体结合结构域与二肉豆蔻酰磷脂酰胆碱形成的盘状复合物具有完全的受体结合活性。人们已经开展了相关研究来表征球状无脂质四螺旋束结构的构象适应性，这种适应性最终导致其两亲性α螺旋与脂质表面稳定结合。双层盘状复合物中的螺旋-脂质相互作用可以想象有两种取向：平行或垂直于磷脂酰基链。基于红外二色性、几何学论据和X射线晶体学的证据支持这样一种观点，即四螺旋束中特定的螺旋片段在与脂质结合时会重新排列，垂直于磷脂脂肪酰链定向，环绕双层盘状结构。因此，成对的螺旋片段很可能串联排列，呈现出一个凸起的受体活性表面。
