Pawar Aiswarya B, Sengupta Durba
CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411 008, India.
Academy of Scientific and Innovative Research, New Delhi, India.
J Membr Biol. 2018 Jun;251(3):359-368. doi: 10.1007/s00232-018-0015-1. Epub 2018 Jan 19.
The association of single transmembrane receptors, such as the ErbB receptors is a key event in initiating cell signaling networks. The interactions between these receptors have been well characterized for both ligand-driven and pre-formed dimers. However, the role of the membrane in modulating association is less well understood and assumes greater importance in light of altered membrane composition in diseased states. Here, we discuss how membrane composition has been observed to induce both structural and dynamic differences in receptor association. Computational studies, especially those using coarse-grain simulations have been successful in predicting the role of the membrane and calculating the related free energy landscapes. Membrane perturbations and differences in lipid chain order, related to the lipophobic effect, have been shown to play a large role in driving membrane protein association. Further, we review lipid compositions reported in diseased conditions and its effect on transmembrane receptor association, focusing on the ErbB growth factor receptor dimers in cancer. Understanding the role of the membrane in receptor association will provide general design principles driving receptor organization, as well as help to identify novel therapeutic strategies.
单跨膜受体（如表皮生长因子受体（ErbB）家族受体）的缔合是启动细胞信号网络的关键事件。这些受体之间的相互作用在配体驱动的二聚体和预形成的二聚体中都已有充分的表征。然而，膜在调节受体缔合中的作用尚不太清楚，鉴于疾病状态下膜组成的改变，这一作用显得更为重要。在这里，我们讨论了膜组成如何诱导受体缔合在结构和动力学上的差异。计算研究，特别是那些使用粗粒度模拟的研究，已经成功地预测了膜的作用并计算了相关的自由能景观。膜扰动以及与疏脂效应相关的脂链有序性差异，已被证明在驱动膜蛋白缔合中起很大作用。此外，我们综述了疾病状态下报道的脂质组成及其对跨膜受体缔合的影响，重点关注癌症中的表皮生长因子受体二聚体。了解膜在受体缔合中的作用将提供驱动受体组织的一般设计原则，并有助于确定新的治疗策略。
