Róg Tomasz, Murzyn Krzysztof, Karttunen Mikko, Pasenkiewicz-Gierula Marta
Biophysics and Statistical Mechanics Group, Faculty of Electrical and Communications Engineering, Helsinki University of Technology, Finland.
J Pept Sci. 2008 Apr;14(4):374-82. doi: 10.1002/psc.936.
A molecular dynamics simulation study of four lipid bilayers with inserted trans-membrane helical fragment of epithelial growth factor (EGF) receptor (EGF peptide) was performed. The lipid bilayers differ in their lipid composition and consist of (i) unsaturated phosphatidylcholine (palmitoyloleoylphosphatidylcholine, POPC), (ii) POPC and 20 mol% of cholesterol (Chol), (iii) sphingomyelin (SM) and 20 mol% of Chol, and (iv) SM and 50 mol% of Chol. Only 1 out of 26 residues in the EGF-peptide sequence is polar (Thr). The hydrophobic thickness of each bilayer is different but shorter than the length of the peptide and so, due to hydrophobic mismatch, the inserted peptide is tilted in each bilayer. Additionally, in the POPC bilayer, which is the thinnest, the peptide loses its helical structure in a short three-amino acid fragment. This facilitates bending of the peptide and burying all hydrophobic amino acids inside the membrane core (Figure 1(b)). Bilayer lipid composition affects interactions between the peptide and lipids in the membrane core. Chol increases packing of atoms relative to the peptide side chains, and thus increases van der Waals interactions. On average, the packing around the peptide is higher in SM-based bilayers than POPC-based bilayers but for certain amino acids, packing depends on their position relative to the bilayer center. In the bilayer center, packing is higher in POPC-based bilayers, while in regions closer to the interface packing is higher in SM-based bilayers. In general, amino acids with larger side chains interact strongly with lipids, and thus the peptide sequence is important for the pattern of interactions at different membrane depths. This pattern closely resembles the shape of recently published lateral pressure profiles [Ollila et alJ. Struct. Biol. DOI:10.1016/j.jsb.2007.01.012].
进行了一项分子动力学模拟研究，该研究针对含有上皮生长因子（EGF）受体跨膜螺旋片段（EGF肽）的四个脂质双层。这些脂质双层的脂质组成不同，分别由（i）不饱和磷脂酰胆碱（棕榈酰油酰磷脂酰胆碱，POPC）、（ii）POPC和20摩尔%的胆固醇（Chol）、（iii）鞘磷脂（SM）和20摩尔%的Chol以及（iv）SM和50摩尔%的Chol组成。EGF肽序列中的26个残基中只有1个是极性的（苏氨酸）。每个双层的疏水厚度不同，但比肽的长度短，因此，由于疏水不匹配，插入的肽在每个双层中都是倾斜的。此外，在最薄的POPC双层中，肽在一个短的三氨基酸片段中失去了其螺旋结构。这有利于肽的弯曲，并将所有疏水氨基酸埋入膜核心内部（图1（b））。双层脂质组成影响肽与膜核心中脂质之间的相互作用。Chol相对于肽侧链增加了原子的堆积，从而增加了范德华相互作用。平均而言，基于SM的双层中肽周围的堆积比基于POPC的双层更高，但对于某些氨基酸，堆积取决于它们相对于双层中心的位置。在双层中心，基于POPC的双层中堆积更高，而在更靠近界面的区域，基于SM的双层中堆积更高。一般来说，具有较大侧链的氨基酸与脂质强烈相互作用，因此肽序列对于不同膜深度处的相互作用模式很重要。这种模式与最近发表的侧向压力分布形状非常相似[奥利拉等人，《结构生物学杂志》，DOI:10.1016/j.jsb.2007.01.012]。
