Brasseur R
Laboratoire Chimie Physique des Macromolecules aux Interfaces CP 206-2, Université Libre de Bruxelles, Belgium.
J Biol Chem. 1991 Aug 25;266(24):16120-7.
Several types of lipid-associating helices exist: transmembrane helices such as in receptor proteins, pore-forming helices in ion channel proteins, fusion-inducing peptides in viral proteins, and amphipathic helices such as in plasma apolipoproteins. In order to propose a classification of these helices according to their molecular properties, we introduce the concept of molecular hydrophobicity potential for such helical segments. The calculation of this parameter for alpha-helices enables the visualization of the hydrophobic and hydrophilic envelopes around the peptide and their three-dimensional representation by molecular graphics. We have used this parameter to differentiate between pore-forming helices with a hydrophobic envelope larger than the hydrophilic component, membrane-spanning helices surrounded almost entirely by an hydrophobic envelope, fusiogenic peptides with an hydrophobicity gradient both around the helix and along the axis, and finally, amphipathic helices with a predominantly hydrophilic envelope. The structure of the lipid-protein complexes is determined by a number of different interactions: the hydrophobic interaction of the apolar faces of the helices with lipids, the polar interaction of the hydrophilic sides of different helices with each other, and the interaction of hydrophilic residues with the aqueous solvent. The relative magnitude of the hydrophobic and hydrophilic envelopes accounts for the differences in the structure of the lipid-protein complexes. Purely hydrophobic interactions stabilize transmembrane helical segments, while hydrophobic interactions with the lipid phase and with each other are involved in the stabilization of the pore-forming helices. In contrast, both hydrophobic interactions with the lipids and hydrophilic interactions with the aqueous phase contribute to the arrangement of amphipathic helices around the edges of the discoidal lipid-apoprotein complexes.
如受体蛋白中的跨膜螺旋、离子通道蛋白中的成孔螺旋、病毒蛋白中的融合诱导肽以及血浆载脂蛋白中的两亲性螺旋。为了根据这些螺旋的分子特性提出一种分类方法，我们引入了此类螺旋片段的分子疏水势概念。对α螺旋计算该参数能够可视化肽周围的疏水和亲水包络，并通过分子图形对其进行三维表示。我们利用这个参数区分了疏水包络大于亲水成分的成孔螺旋、几乎完全被疏水包络包围的跨膜螺旋、螺旋周围和沿轴都有疏水梯度的融合肽，以及最后主要具有亲水包络的两亲性螺旋。脂质 - 蛋白质复合物的结构由多种不同的相互作用决定：螺旋的非极性面与脂质的疏水相互作用、不同螺旋的亲水侧之间的极性相互作用，以及亲水残基与水性溶剂的相互作用。疏水和亲水包络的相对大小解释了脂质 - 蛋白质复合物结构的差异。纯粹的疏水相互作用稳定跨膜螺旋片段，而成孔螺旋的稳定则涉及与脂质相以及彼此之间的疏水相互作用。相比之下，与脂质的疏水相互作用和与水相的亲水相互作用都有助于两亲性螺旋围绕盘状脂质 - 载脂蛋白复合物边缘的排列。
