Direct observation of a coil-to-helix contraction triggered by vinculin binding to talin
Direct observation of a coil-to-helix contraction triggered by vinculin binding to talin
复制标题
DOI：
10.1126/sciadv.aaz4707
复制
发表时间：
2020-05-01
期刊：
影响因子：
13.6
通讯作者：
Fernandez, Julio
中科院分区：
文献类型：
--
作者：
Tapia-Rojo, Rafael;Alonso-Caballero, Alvaro;Fernandez, Julio
纽蛋白在局部粘连中结合未折叠的Talin结构域，从而招募肌动蛋白细丝来加强该细胞器的机械耦合。然而，目前还不清楚这种相互作用是如何调节的，以及它对这一机械转导途径的力传递特性的影响。在这里，我们使用磁钳来测量在生理作用力下纽蛋白头部和Talin R3结构域之间的相互作用。我们首次将单个结合事件解析为由纽蛋白结合位点螺旋的改造引起的未折叠Talin多肽的短暂收缩，这决定了一种调节这种相互作用的双相机制。力通过展开talin和暴露vinculin结合位点而有利于vinculin结合；然而，螺旋到螺旋的收缩引入了随力增加的能量惩罚，定义了最佳结合制度。这一机制暗示Talin-vinculin-actin联合作用可能作为一种负反馈机制来稳定局灶性粘连的作用力。
Vinculin binds unfolded talin domains in focal adhesions, which recruits actin filaments to reinforce the mechanical coupling of this organelle. However, it remains unknown how this interaction is regulated and its impact on the force transmission properties of this mechanotransduction pathway. Here, we use magnetic tweezers to measure the interaction between vinculin head and the talin R3 domain under physiological forces. For the first time, we resolve individual binding events as a short contraction of the unfolded talin polypeptide caused by the reformation of the vinculin-binding site helices, which dictates a biphasic mechanism that regulates this interaction. Force favors vinculin binding by unfolding talin and exposing the vinculin-binding sites; however, the coil-to-helix contraction introduces an energy penalty that increases with force, defining an optimal binding regime. This mechanism implies that the talin-vinculin-actin association could operate as a negative feedback mechanism to stabilize force on focal adhesions.