Rate limit of protein elastic response is tether dependent
Rate limit of protein elastic response is tether dependent
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DOI：
10.1073/pnas.1212167109
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发表时间：
2012-09-04
影响因子：
11.1
通讯作者：
Fernandez, Julio M.
中科院分区：
文献类型：
--
作者：
Berkovich, Ronen;Hermans, Rodolfo I.;Fernandez, Julio M.
组织的弹性恢复力必须能够在生物体所经历的非常宽的加载速率范围内起作用。令人惊讶的是，即使是涉及动物肌肉组织的最快事件也不会超过几百赫兹。我们建议，这一限制是由拴系蛋白质的弹性动力学在不断变化的负载下延伸和放松。在这里，我们研究的弹性动力学系留蛋白质使用快速力谱仪与亚毫秒的时间分辨率，结合布朗和分子动力学模拟。我们表明，拴系多肽的对象，在体内和实验设置中的蛋白质弹性的一个不可分割的部分，大大降低了尝试频率与蛋白质样品的自由能的行为。事实上，我们的数据表明，拴系的多肽可以以令人惊讶的低有效扩散系数D-eff（类似于1,200 nm（2）/s）穿越其自由能景观。相比之下，我们的分子动力学模拟表明，在力的作用下，分离的蛋白质的扩散发生在类似于10（8）nm 2/s的D-eff。这种差异归因于系留物体引起的拖曳力。从组织弹性的生理时间尺度，我们计算出束缚的弹性蛋白质在体内平衡，D-eff类似于10（4）-10（6）nm 2/s，这比未束缚的蛋白质在本体中测量的值小两到四个数量级。
The elastic restoring force of tissues must be able to operate over the very wide range of loading rates experienced by living organisms. It is surprising that even the fastest events involving animal muscle tissues do not surpass a few hundred hertz. We propose that this limit is set in part by the elastic dynamics of tethered proteins extending and relaxing under a changing load. Here we study the elastic dynamics of tethered proteins using a fast force spectrometer with sub-millisecond time resolution, combined with Brownian and Molecular Dynamics simulations. We show that the act of tethering a polypeptide to an object, an inseparable part of protein elasticity in vivo and in experimental setups, greatly reduces the attempt frequency with which the protein samples its free energy. Indeed, our data shows that a tethered polypeptide can traverse its free-energy landscape with a surprisingly low effective diffusion coefficient D-eff similar to 1,200 nm(2)/s. By contrast, our Molecular Dynamics simulations show that diffusion of an isolated protein under force occurs at D-eff similar to 10(8) nm2/s. This discrepancy is attributed to the drag force caused by the tethering object. From the physiological time scales of tissue elasticity, we calculate that tethered elastic proteins equilibrate in vivo with D-eff similar to 10(4)-10(6) nm2/s which is two to four orders magnitude smaller than the values measured for untethered proteins in bulk.