Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus C, Denmark.
Nat Commun. 2011;2:304. doi: 10.1038/ncomms1307.
The structural elucidation of membrane proteins continues to gather pace, but we know little about their molecular interactions with the lipid environment or how they interact with the surrounding bilayer. Here, with the aid of low-resolution X-ray crystallography, we present direct structural information on membrane interfaces as delineated by lipid phosphate groups surrounding the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) in its phosphorylated and dephosphorylated Ca(2+)-free forms. The protein-lipid interactions are further analysed using molecular dynamics simulations. We find that SERCA adapts to membranes of different hydrophobic thicknesses by inducing local deformations in the lipid bilayers and by undergoing small rearrangements of the amino-acid side chains and helix tilts. These mutually adaptive interactions allow smooth transitions through large conformational changes associated with the transport cycle of SERCA, a strategy that may be of general nature for many membrane proteins.
膜蛋白的结构阐明工作仍在不断加速，但我们对它们与脂质环境的分子相互作用以及它们与周围双层的相互作用知之甚少。在这里，借助低分辨率 X 射线晶体学，我们呈现了直接的结构信息，展示了围绕肌浆（内质）网 Ca2+-ATP 酶（SERCA）的磷酸化和去磷酸化 Ca2+-自由形式的磷酸脂基团所描绘的膜界面。使用分子动力学模拟进一步分析了蛋白质-脂质相互作用。我们发现，SERCA 通过诱导脂质双层的局部变形以及氨基酸侧链和螺旋倾斜的小重排，适应不同疏水性厚度的膜。这些相互适应的相互作用允许通过与 SERCA 运输循环相关的大构象变化进行平稳过渡，这一策略可能对许多膜蛋白具有普遍意义。
