Department of Biochemistry of Membranes, Center for Biomembranes and Lipid Enzymology, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
J Membr Biol. 2010 Apr;234(3):235-40. doi: 10.1007/s00232-010-9251-8. Epub 2010 Mar 30.
In this study, the roles of two anionic phospholipids-phosphatidic acid (PA), which is an important signaling molecule, and cardiolipin (CL), which plays a crucial role in the bioenergetics of the cell-in stabilizing the oligomeric structure of potassium channel KcsA were determined. The stability of KcsA was drastically increased as a function of PA or CL content (mol%) in phosphatidylcholine (PC) bilayers. Deletion of the membrane-associated N terminus significantly reduced channel stability at high levels of PA content; however, the intrinsic stability of this protein was marginally affected in the presence of CL. These studies indicate that the electrostatic-hydrogen bond switch between PA and N terminus, involving basic residues, is much stronger than the stabilizing effect of CL. Furthermore, the unique properties of the PA headgroup alter protein assembly and folding properties differently from the CL headgroup, and both lipids stabilize the tetrameric assembly via their specific interaction on the extra- or the intracellular side of KcsA.
在这项研究中，确定了两种阴离子磷脂 - 磷脂酸（PA）和心磷脂（CL）在稳定钾通道 KcsA 的寡聚结构中的作用。PA 或 CL 的含量（mol％）在磷脂酰胆碱（PC）双层中增加了 KcsA 的稳定性。与高 PA 含量相比，膜相关 N 末端的缺失显著降低了通道稳定性; 然而，在 CL 存在下，该蛋白质的固有稳定性仅受到轻微影响。这些研究表明，PA 和 N 末端之间的静电氢键开关，涉及碱性残基，比 CL 的稳定作用强得多。此外，PA 头部基团的独特性质与 CL 头部基团不同地改变蛋白质组装和折叠性质，并且两种脂质都通过其在 KcsA 的细胞外或细胞内侧的特定相互作用来稳定四聚体组装。
