Osten Veronika, Schneider Dirk
Department of Chemistry, Biochemistry, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Department of Chemistry, Biochemistry, Johannes Gutenberg University Mainz, 55128 Mainz, Germany; Institute of Molecular Physiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Biochim Biophys Acta Biomembr. 2025 Jun;1867(5-6):184430. doi: 10.1016/j.bbamem.2025.184430. Epub 2025 Jun 17.
The structure and the function of membrane proteins can be affected by the lipid bilayer environment, yet its impact is often neglected in in vitro studies where proteins are typically analyzed in membrane mimetics, mostly liposomal systems. It has been observed that the activity of the bacterial ATP-binding cassette (ABC) transporter BmrA (Bacillus multidrug resistance ATP) differs when measured in detergent vs. a model membrane environment, indicating that the physico-chemical properties of the membrane environment crucially affect the protein's activity. We now performed a systematic analysis to elucidate the impact of individual lipid/membrane properties on the activity of BmrA and identified three parameters controlling the BmrA activity in lipid bilayers: (i) the hydrophobic thickness of the membrane, (ii) a negative surface charge, and (iii) the packing of lipids in the acyl-chain and head group regions. Our study provides valuable insights into how a specific lipid composition can influence the basal ATPase activity of BmrA and emphasizes that the lipid composition should be carefully selected in in vitro studies of membrane proteins.
膜蛋白的结构和功能会受到脂质双层环境的影响，然而在体外研究中这种影响常常被忽视，在体外研究中，蛋白质通常在膜模拟物（主要是脂质体系统）中进行分析。据观察，细菌ATP结合盒（ABC）转运蛋白BmrA（芽孢杆菌多药耐药ATP）在去污剂环境与模型膜环境中测量时活性不同，这表明膜环境的物理化学性质对蛋白质活性有至关重要的影响。我们现在进行了一项系统分析，以阐明单个脂质/膜特性对BmrA活性的影响，并确定了控制脂质双层中BmrA活性的三个参数：（i）膜的疏水厚度，（ii）负表面电荷，以及（iii）酰基链和头部基团区域中脂质的堆积。我们的研究为特定脂质组成如何影响BmrA的基础ATP酶活性提供了有价值的见解，并强调在膜蛋白的体外研究中应仔细选择脂质组成。
