Physik Department E22, Technische Universität München, 85748 Garching, Germany.
Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1015-1020. doi: 10.1073/pnas.1612681114. Epub 2017 Jan 17.
Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.
肌节 Z 盘内肌联蛋白的稳定锚定对于在被动拉伸过程中保持肌肉完整性至关重要。锚定肌联蛋白在 Z 盘的主要候选物之一是肌动蛋白交联蛋白α-辅肌动蛋白。α-辅肌动蛋白的钙调蛋白样结构域与肌联蛋白的 Z 重复序列结合。然而，这种重要相互作用的机械和动力学特性仍然未知。在这里，我们使用双光束光镊测定法在单分子水平上研究这种相互作用的力学性质。如果施加力，单个α-辅肌动蛋白和肌联蛋白的相互作用实际上非常弱。根据力的施加方向，解结合力可以增加三倍以上。我们的结果表明，在确保肌联蛋白长期稳定锚定的同时，允许单个成分动态交换的模型中，多个α-辅肌动蛋白/Z 重复相互作用共同起作用。
