A new direction for titin pulling.
A new direction for titin pulling.
复制标题
提汀拉动的新方向。
DOI：
10.1073/pnas.0906989106
复制
发表时间：
2009
影响因子：
11.1
通讯作者：
Rock,RonaldS
中科院分区：
文献类型：
--
作者：
Rock,RonaldS
已知许多蛋白质在细胞和组织中起结构支架的作用。这些蛋白质维持细胞的形状，充当局部力传感器，对于形成暴露在巨大外力下的组织是必不可少的。尽管这些结构蛋白看似被动，但它们具有独特的物理特征，值得仔细研究。特别是，了解支架蛋白质和蛋白质复合体如何响应生物学中常见的高外力是至关重要的。在这一期的PNAS中，Bertz等人(1)报告了这些承载复合体的一个显著的新特征。显然，进化已经塑造了这些蛋白质，当它们被拉向与它们在细胞中所经历的相同的方向时，它们对展开具有显著的抵抗力。然而，在其他拉动方向上，该复合体相对脆弱。Bertz等人(1)在Titin及其结合伙伴--端乙醇胺(1)的复合体中发现了这些“定向键”。肌动蛋白是一种在肌肉肌节中发现的巨大蛋白质，它有助于肌肉的组织和被动弹性(2，3)。两个Titin分子通过其N端的反平行排列被锚定在肌节Z盘处。在这个N-末端重叠区发现Telethonin，它与每个Titin分子(4)的两个Ig结构域Z1和Z2结合(见图1)。整个N末端复合体必须特别坚固，才能承受肌肉中的巨大力量。Bertz等人(1)专注于这种2：1的Titin Z1Z2：telthonin复合体，使用原子力显微镜来拉开并机械地展开该复合体。利用连接在两个Z2结构域C-末端的手柄，他们将复合体拉向一个模仿肌节内伸展方向的方向。他们的发现令人惊讶：这不仅是有史以来测量到的最强大的蛋白质或蛋白质复合体，而且它还可以承受打破共价键所需的近一半的力。显然，这个综合体有一些不同寻常的特征，导致它具有非凡的稳定性。更令人惊讶的是，Bertz等人(1)发现这种稳定性依赖于
Many proteins are known to serve roles as structural scaffolds in cells and tissues. These proteins maintain the shape of the cell, act as local force sensors, and are essential to form tissues that are exposed to large external forces. Although seemingly passive elements, these structural proteins have unique physical features that are worthy of a closer look. In particular, it is critically important to understand how scaffolding proteins and protein complexes respond to the high external forces commonly encountered in biology. In this issue of PNAS, Bertz et al.(1) report a remarkable new feature of these load-bearing complexes. Apparently, evolution has molded these proteins to be remarkably resistant to unfolding when pulled in the same direction as they would experience in the cell. However, in other pulling directions the complex is relatively fragile.Bertz et al.(1) found these ‘‘directional bonds’’in a complex of titin and its binding partner, telethonin (1). Titin is an enormous protein found in muscle sarcomeres, where it contributes to the organization and passive elasticity of muscle (2, 3). Two titin molecules are anchored together at the sarcomere Z-disk through an antiparallel arrangement of their N-terminal ends. Telethonin is found at this N-terminal overlap region, where it binds to two Ig domains, Z1 and Z2, from each titin molecule (4)(see Fig. 1). This whole N-terminal complex must be particularly robust to withstand the large forces found in muscle. Bertz et al.(1) focused in on this 2: 1 titin Z1Z2: telethonin complex, using an atomic force microscope to pull on and mechanically unfold the complex. Using handles attached to the C-terminal ends of the two Z2 domains, they pulled on the complex in a direction that would mimic the stretching direction within a sarcomere. What they found was surprising: not only was this the most robust protein or protein complex ever measured, but it also could withstand nearly half the force required to break a covalent bond. Clearly, there are some unusual features of this complex that lead to its remarkable stability. Even more surprising, Bertz et al.(1) found that this stability depended