Jepson Tyler A, Hall Sarah C, Chung Jean K
Colorado State University, Fort Collins, Colorado.
Colorado State University, Fort Collins, Colorado.
Biophys J. 2022 Apr 19;121(8):1417-1423. doi: 10.1016/j.bpj.2022.03.019. Epub 2022 Mar 18.
While it is established that the topology of lipid membranes plays an important role in biochemical processes, few direct observations exist regarding how the membranes are actively restructured and its consequences on subsequent reactions. In this work, we investigated how the two major components of bee venom, melittin and phospholipase A (PLA), achieve activation by such membrane remodeling. Their membrane-disrupting functions have been reported to increase when both are present, but the mechanism of this synergism had not been established. Using membrane reconstitution, we found that melittin can form large-scale membrane deformities upon which PLA activity is 25-fold higher. Tracking of single-molecule PLA revealed that its processive behavior on these deformities underlies the enhanced activity. These results show how melittin and PLA work synergistically to enhance the lytic effects of the bee venom. More broadly, they also demonstrate how the membrane topology may be actively altered to modulate cellular membrane-bound reactions.
虽然已经确定脂膜的拓扑结构在生化过程中起着重要作用，但关于膜如何被主动重塑及其对后续反应的影响，几乎没有直接的观察结果。在这项工作中，我们研究了蜂毒的两个主要成分蜂毒素和磷脂酶A（PLA）如何通过这种膜重塑实现激活。据报道，当两者都存在时，它们的膜破坏功能会增强，但这种协同作用的机制尚未确定。通过膜重组，我们发现蜂毒素可以形成大规模的膜畸形，在此基础上PLA活性提高25倍。对单分子PLA的追踪表明，其在这些畸形上的持续行为是活性增强的基础。这些结果表明蜂毒素和PLA如何协同作用以增强蜂毒的裂解作用。更广泛地说，它们还展示了膜拓扑结构如何被主动改变以调节细胞膜结合反应。
