School of Chemistry and Molecular Biosciences, The University of Queensland , Brisbane QLD 4072, Australia.
J Phys Chem B. 2013 Dec 19;117(50):16129-40. doi: 10.1021/jp409748d. Epub 2013 Dec 3.
Sterols are the hallmarks of eukaryotic membranes where they are often found in specialized functional microdomains of the plasma membrane called lipid rafts. Despite some notable exceptions, prokaryotes lack sterols. However, growing evidence has suggested the existence of raft-like domains in the plasma membrane of bacteria. A structurally related family of triterpenoids found in some bacteria called hopanoids has long been assumed to be bacterial surrogates for sterols in membranes. Although the effect of sterols, in particular cholesterol, on lipid bilayers has been extensively characterized through experimental and simulation studies, those of hopanoids have hardly been investigated. In this study, molecular dynamics simulations are used to examine the effect of two hopanoids, diploptene (hop-22(29)-ene) and bacteriohopanetetrol ((32R,33S,34S)-bacteriohopane-32,33,34,35-tetrol), on a model bilayer. The results are compared with those obtained for cholesterol and a pure phosphatidylcholine bilayer. It is shown that diploptene and bacteriohopanetetrol behave very differently under the conditions simulated. Whereas bacteriohopanetetrol adopted a cholesterol-like upright orientation in the bilayer, diploptene partitioned between the two leaflets inside the bilayer. Analysis of various structural properties (area per lipid, electron density profile, tilt angle of the lipids, and conformation and order parameters of the phosphatidylcholine tails) in bacteriohopanetetrol- and cholesterol-containing bilayers indicates that the condensing and ordering effect of bacteriohopanetetrol is weaker than that of cholesterol. The simulations suggest that the chemical diversity of hopanoids may lead to a broader range of functional roles in bacterial membranes than sterols in eukaryotic membranes.
甾醇是真核生物膜的标志，它们通常存在于质膜的专门功能微区，称为脂筏。尽管存在一些显著的例外，原核生物缺乏甾醇。然而，越来越多的证据表明细菌质膜中存在类似筏的结构域。在一些细菌中发现的一种结构相关的三萜类化合物家族称为藿烷类化合物，长期以来一直被认为是膜中甾醇的细菌替代物。尽管甾醇，特别是胆固醇，对脂质双层的影响已经通过实验和模拟研究得到了广泛的描述，但藿烷类化合物的影响几乎没有被研究过。在这项研究中，使用分子动力学模拟来研究两种藿烷类化合物，双萜（hop-22(29)-ene）和细菌藿烷四醇（(32R,33S,34S)-细菌藿烷-32,33,34,35-四醇）对模型双层的影响。将结果与胆固醇和纯磷脂双层的结果进行比较。结果表明，在模拟条件下，双萜和细菌藿烷四醇的行为非常不同。虽然细菌藿烷四醇在双层中采取类似于胆固醇的直立取向，但双萜在双层内部的两个叶层之间分配。对各种结构性质（每个脂质的面积、电子密度分布、脂质的倾斜角以及磷脂酰胆碱尾部的构象和序参数）进行分析，表明细菌藿烷四醇的凝结和有序化效应比胆固醇弱。模拟表明，藿烷类化合物的化学多样性可能导致细菌膜中具有比真核生物膜中甾醇更广泛的功能作用。
