Cellular Machines Group, Biotechnology Center, TU Dresden, 01307 Dresden, Germany.
Structure. 2010 Jan 13;18(1):39-46. doi: 10.1016/j.str.2009.11.009.
Mitochondrial ADP/ATP carriers are inhibited by two natural compounds, atractyloside (ATR) or carboxy-atractyloside (CATR), which differ by one carboxylate group. The interactions of the inhibitors with the carrier were investigated by single-molecule force spectroscopy. Transmembrane alpha helices of the ATR-inhibited carrier displayed heterogeneous mechanical and kinetic properties. Whereas alpha helix H2 showed the most brittle mechanical properties and lowest kinetic stability, alpha helix H5 was mechanically the most flexible and possessed a kinetic stability 9 orders of magnitude greater than that of alpha helix H2. In contrast, CATR-binding substantially increased the kinetic stability of alpha helix H2 and tuned the mechanical flexibility of alpha helices H5 and H6. NMR spectroscopy confirmed that the additional carboxylate group of CATR binds to the sixth alpha helix, indicating that the enhanced stability of H2 is mediated via interactions between CATR and H6.
线粒体 ADP/ATP 载体被两种天然化合物，苍术苷（ATR）或羧基苍术苷（CATR）抑制，它们仅相差一个羧基。通过单分子力谱研究了抑制剂与载体的相互作用。ATR 抑制的载体的跨膜α螺旋表现出不均匀的力学和动力学特性。虽然α螺旋 H2 表现出最脆的力学特性和最低的动力学稳定性，但α螺旋 H5 在力学上是最灵活的，并且具有比α螺旋 H2 高 9 个数量级的动力学稳定性。相比之下，CATR 结合大大增加了α螺旋 H2 的动力学稳定性，并调节了α螺旋 H5 和 H6 的力学灵活性。NMR 光谱证实，CATR 的额外羧基结合到第六个α螺旋，表明 H2 的稳定性增强是通过 CATR 和 H6 之间的相互作用介导的。
