Zhang Yue, Zhu Xiaohong, Zhang Honghui, Yan Junfang, Xu Peiyi, Wu Peng, Wu Song, Bai Chen
School of Life and Health Sciences, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.
School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China.
Membranes (Basel). 2022 Jul 7;12(7):694. doi: 10.3390/membranes12070694.
Membrane proteins play crucial roles in various physiological processes, including molecule transport across membranes, cell communication, and signal transduction. Approximately 60% of known drug targets are membrane proteins. There is a significant need to deeply understand the working mechanism of membrane proteins in detail, which is a challenging work due to the lack of available membrane structures and their large spatial scale. Membrane proteins carry out vital physiological functions through conformational changes. In the current study, we utilized a coarse-grained (CG) model to investigate three representative membrane protein systems: the TMEM16A channel, the family C GPCRs mGlu2 receptor, and the P4-ATPase phospholipid transporter. We constructed the reaction pathway of conformational changes between the two-end structures. Energy profiles and energy barriers were calculated. These data could provide reasonable explanations for TMEM16A activation, the mGlu2 receptor activation process, and P4-ATPase phospholipid transport. Although they all belong to the members of membrane proteins, they behave differently in terms of energy. Our work investigated the working mechanism of membrane proteins and could give novel insights into other membrane protein systems of interest.
膜蛋白在各种生理过程中发挥着关键作用，包括分子跨膜运输、细胞通讯和信号转导。已知约60%的药物靶点是膜蛋白。深入详细了解膜蛋白的工作机制具有重大需求，由于缺乏可用的膜结构及其较大的空间尺度，这是一项具有挑战性的工作。膜蛋白通过构象变化执行重要的生理功能。在当前研究中，我们利用粗粒度（CG）模型研究了三个代表性的膜蛋白系统：TMEM16A通道、C类G蛋白偶联受体mGlu2受体和P4-ATPase磷脂转运蛋白。我们构建了两端结构之间构象变化的反应途径。计算了能量分布和能垒。这些数据可以为TMEM16A激活、mGlu2受体激活过程和P4-ATPase磷脂转运提供合理的解释。尽管它们都属于膜蛋白成员，但在能量方面表现不同。我们的工作研究了膜蛋白的工作机制，并可为其他感兴趣的膜蛋白系统提供新的见解。
