Presti F T, Pace R J, Chan S I
Biochemistry. 1982 Aug 3;21(16):3831-5. doi: 10.1021/bi00259a017.
A model for the molecular interaction between cholesterol and phospholipid in bilayer membranes is presented. We propose that cholesterol forms associations with phospholipids with stoichiometries of both 1:1 and 1:2. A hydrogen bond between the beta-OH of cholesterol and the glycerol ester oxygen of a phospholipid is suggested as a likely mechanism for tight binding in a 1:1 complex. A second phospholipid molecule is loosely associated with the complex to form domains of 1:2 stoichiometry, which may coexist with pure phospholipid domains. Interfacial boundary phospholipid separates these two domains. Under conditions in which interfacial phospholipid is maximal, the perturbed phospholipid assumes a composition of 20 mol % cholesterol. To account for the phase behavior and surface properties of cholesterol-lipid membranes, we propose a molecular packing model for linear arrays within the cholesterol-rich domains. In this arrangement, two rows of 1:1 complex run antiparallel with loosely associated phospholipid intercalated between them. The loosely associated phospholipid can pack in the nearly hexagonal manner in which pure crystalline phospholipid is known to pack. The model provides maximal van der Waals contact in the hydrocarbon region of the bilayer and can maintain phospholipids as cholesterol's nearest neighbors at all concentrations up to 50 mol % cholesterol. The model is compatible with the diverse experimental observations compiled by many investigators over the past decade.
本文提出了一种双层膜中胆固醇与磷脂分子相互作用的模型。我们认为胆固醇与磷脂形成化学计量比为1:1和1:2的缔合物。胆固醇的β-OH与磷脂的甘油酯氧之间的氢键被认为是1:1复合物中紧密结合的可能机制。第二个磷脂分子与该复合物松散缔合，形成化学计量比为1:2的结构域，其可能与纯磷脂结构域共存。界面边界磷脂将这两个结构域分隔开。在界面磷脂最大的条件下，受扰动的磷脂的组成是20摩尔%的胆固醇。为了解释胆固醇-脂质膜的相行为和表面性质，我们提出了一种富含胆固醇区域内线性阵列的分子堆积模型。在这种排列中，两排1:1复合物反平行排列，其间夹着松散缔合的磷脂。松散缔合的磷脂可以以已知纯结晶磷脂堆积的近乎六边形的方式堆积。该模型在双层膜的烃区域提供了最大的范德华接触，并且在胆固醇浓度高达50摩尔%的所有浓度下都能使磷脂保持为胆固醇的最近邻。该模型与许多研究人员在过去十年中汇编的各种实验观察结果一致。
