PDF(Pubmed)
Abstract：
Using the gramicidin A channel as a molecular probe, we show that tubulin binding to planar lipid membranes changes the channel kinetics-seen as an increase in the lifetime of the channel dimer-and thus points towards modification of the membrane\'s mechanical properties. The effect is more pronounced in the presence of non-lamellar lipids in the lipid mixture used for membrane formation. To interpret these findings, we propose that tubulin binding redistributes the lateral pressure of lipid packing along the membrane depth, making it closer to the profile expected for lamellar lipids. This redistribution happens because tubulin perturbs the lipid headgroup spacing to reach the membrane\'s hydrophobic core via its amphiphilic α-helical domain. Specifically, it increases the forces of repulsion between the lipid headgroups and reduces such forces in the hydrophobic region. We suggest that the effect is reciprocal, meaning that alterations in lipid bilayer mechanics caused by membrane remodeling during cell proliferation in disease and development may also modulate tubulin membrane binding, thus exerting regulatory functions. One of those functions includes the regulation of protein-protein interactions at the membrane surface, as exemplified by VDAC complexation with tubulin.
摘要：
使用小草素A通道作为分子探针，我们表明，微管蛋白与平面脂质膜的结合改变了通道动力学-被视为通道二聚体寿命的增加-因此指向了膜的机械性能的改变。在用于膜形成的脂质混合物中存在非层状脂质的情况下，该作用更加明显。为了解释这些发现，我们提出微管蛋白结合沿着膜深度重新分布脂质填充的侧压，使其更接近层状脂质的预期轮廓。发生这种重新分布是因为微管蛋白干扰脂质头基间距，通过其两亲性α-螺旋结构域到达膜的疏水核。具体来说,它增加了脂质头基之间的排斥力，并减少了疏水区域中的这种力。我们认为效果是互惠的，这意味着在疾病和发育过程中细胞增殖过程中由膜重塑引起的脂质双层力学的改变也可能调节微管蛋白膜结合，从而发挥监管功能。这些功能之一包括调节膜表面的蛋白质-蛋白质相互作用，例如VDAC与微管蛋白的络合。
