Wieprecht Torsten, Beyermann Michael, Seelig Joachim
Department of Biophysical Chemistry, Biozentrum University of Basel, Basel, Switzerland.
Biophys Chem. 2002 May 2;96(2-3):191-201. doi: 10.1016/s0301-4622(02)00025-x.
The binding of peptides or proteins to a bilayer membrane is often coupled with a random coil-->alpha-helix transition. Knowledge of the energetics of this membrane-induced folding event is essential for the understanding of the mechanism of membrane activity. In a recent study [Wieprecht et al., J. Mol. Biol. 294 (1999) 785-794], we have developed an approach which allows an analysis of the energetics of membrane-induced folding. We have systematically varied the helix content of the amphipathic peptide magainin-2-amide by synthesizing analogs where two adjacent amino acid residues were substituted by their corresponding D-enantiomers and have measured their binding to small unilamellar vesicles (SUVs). Correlation of the binding parameters with the helicities allowed the evaluation of the thermodynamic parameters of helix formation. Since SUVs (30 nm in diameter) are characterized by a non-ideal lipid packing due to their high membrane curvature, we have now extended our studies to large unilamellar vesicles (LUVs) (100 nm in diameter) with a lipid packing close to planar membranes. While the free energy of binding was similar for SUVs and LUVs, the binding enthalpies and entropies were distinctly different for the two membrane systems. The thermodynamic parameters of the coil-helix transition were nevertheless not affected by the vesicle size. Helix formation at the membrane surface of LUVs (SUVs) was characterized by an enthalpy change of -0.8 (-0.7) kcal/mol per residue, an entropy change of-2.3 (-1.9) cal/mol K per residue, and a free energy change of -0.12 (-0.14) kcal/mol per residue. Helix formation accounted for approximately 50% of the free energy of binding underlining its major role as a driving force for membrane-binding.
肽或蛋白质与双层膜的结合通常伴随着无规卷曲向α-螺旋的转变。了解这种膜诱导折叠事件的能量学对于理解膜活性机制至关重要。在最近的一项研究[Wieprecht等人，《分子生物学杂志》294（1999）785 - 794]中，我们开发了一种方法，可用于分析膜诱导折叠的能量学。我们通过合成类似物系统地改变了两亲性肽magainin - 2 -酰胺的螺旋含量，其中两个相邻的氨基酸残基被其相应的D -对映体取代，并测量了它们与小单层囊泡（SUV）的结合。结合参数与螺旋度的相关性使得能够评估螺旋形成的热力学参数。由于SUV（直径30 nm）因其高膜曲率而具有非理想的脂质堆积特征，我们现在已将研究扩展到脂质堆积接近平面膜的大单层囊泡（LUV）（直径100 nm）。虽然SUV和LUV的结合自由能相似，但两种膜系统的结合焓和熵明显不同。然而，无规卷曲 - 螺旋转变 的热力学参数不受囊泡大小的影响。LUV（SUV）膜表面的螺旋形成特征在于每个残基的焓变为 - 0.8（ - 0.7）kcal/mol，每个残基的熵变为 - 2.3（ - 1.9）cal/mol K，每个残基的自由能变为 - 0.12（ - 0.14）kcal/mol。螺旋形成约占结合自由能的50％，突出了其作为膜结合驱动力的主要作用。
