García-Sáez Ana J, Chiantia Salvatore, Salgado Jesús, Schwille Petra
Biotechnologisches Zentrum der TU Dresden, Dresden, Germany.
Biophys J. 2007 Jul 1;93(1):103-12. doi: 10.1529/biophysj.106.100370. Epub 2007 Apr 6.
Bax is a critical regulator of physiological cell death that increases the permeability of the outer mitochondrial membrane and facilitates the release of the so-called apoptotic factors during apoptosis. The molecular mechanism of action is unknown, but it probably involves the formation of partially lipidic pores induced by Bax. To investigate the interaction of Bax with lipid membranes and the physical changes underlying the formation of Bax pores, we used an active peptide derived from helix 5 of this protein (Bax-alpha5) that is able to induce Bax-like pores in lipid bilayers. We report the decrease of line tension due to peptide binding both at the domain interface in phase-separated lipid bilayers and at the pore edge in atomic force microscopy film-rupture experiments. Such a decrease in line tension may be a general strategy of pore-forming peptides and proteins, as it affects the energetics of the pore and stabilizes the open state.
Bax是生理性细胞死亡的关键调节因子，它可增加线粒体外膜的通透性，并在细胞凋亡过程中促进所谓凋亡因子的释放。其分子作用机制尚不清楚，但可能涉及Bax诱导形成的部分脂质孔。为了研究Bax与脂质膜的相互作用以及Bax孔形成背后的物理变化，我们使用了源自该蛋白第5螺旋的活性肽（Bax-α5），它能够在脂质双层中诱导形成类似Bax的孔。我们报告了在相分离脂质双层的结构域界面以及原子力显微镜膜破裂实验中孔边缘处，由于肽结合导致的线张力降低。这种线张力的降低可能是成孔肽和蛋白质的一种普遍策略，因为它影响孔的能量学并稳定开放状态。
