Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
PLoS One. 2012;7(12):e52839. doi: 10.1371/journal.pone.0052839. Epub 2012 Dec 21.
Protein recruitment to specific membrane locations may be governed or facilitated by electrostatic attraction, which originates from a multivalent ligand. Here we explored the energetics of a model system in which this simple electrostatic recruitment mechanism failed. That is, basic poly-L-lysine binding to one leaflet of a planar lipid bilayer did not recruit the triply-charged peptide (O-Pyromellitylgramicidin). Clustering was only observed in cases where PLL was bound to both channel ends. Clustering was indicated (i) by the decreased diffusional PLL mobility D(PLL) and (ii) by an increased lifetime τ(PLL) of the clustered channels. In contrast, if PLL was bound to only one leaflet, neither D(PLL) nor τ(P) changed. Simple calculations suggest that electrostatic repulsion of the unbound ends prevented neighboring OPg dimers from approaching each other. We believe that a similar mechanism may also operate in cell signaling and that it may e.g. contribute to the controversial results obtained for the ligand driven dimerization of G protein-coupled receptors.
蛋白质向特定膜位置的募集可能受到静电吸引的控制或促进，这种静电吸引源自多价配体。在这里，我们研究了一个模型系统的能量学，其中这种简单的静电募集机制失败了。也就是说，带正电荷的多聚 L-赖氨酸结合到平面脂双层的一个叶面上并没有募集到三价肽（O-焦谷氨酸缬氨霉素）。只有在 PLL 结合到通道两端时才观察到聚集。聚集的指示是：(i)扩散 PLL 的迁移率 D(PLL)降低和 (ii)聚集通道的寿命 τ(PLL)增加。相比之下，如果 PLL 只结合到一个叶面上，D(PLL)和 τ(P)都不会改变。简单的计算表明，未结合端的静电排斥阻止了相邻的 OPg 二聚体相互接近。我们相信，类似的机制也可能在细胞信号转导中起作用，并且它可能例如，导致 G 蛋白偶联受体配体驱动二聚化的有争议的结果。
