Gomez David, Huber Klaus, Klumpp Stefan
Max Planck Institute of Colloids and Interfaces , 14476 Potsdam , Germany.
School of Mechanical Engineering , Tel Aviv University , Tel Aviv 6997801 , Israel.
J Phys Chem Lett. 2019 Dec 19;10(24):7650-7656. doi: 10.1021/acs.jpclett.9b02642. Epub 2019 Nov 27.
The interior of a cell is a highly packed environment that can be occupied up to 40% by different macromolecules. Such crowded media influence different biochemical processes like protein folding, enzymatic activity, and gene regulation. In this work, we use simulations to study protein stability under the presence of crowding agents that interact with the protein by excluded volume interactions. In general, the presence of crowding agents in the solution enhances the stability of the protein's native state. However, we find that the effects of excluded volume depend not only on crowding occupancy but also the crowders' geometry and size. Specifically, we find that polymeric crowders have stronger influence than spherical crowders and that this effect increases with polymer length, while it decreases with increasing size of spherical crowders. These opposing size effects are explained by the interplay of decreasing excluded volume and demixing, which together determine the change in the entropy of the crowders upon folding of the protein.
细胞内部是一个高度拥挤的环境，不同的大分子占据了高达40%的空间。这种拥挤的介质会影响不同的生化过程，如蛋白质折叠、酶活性和基因调控。在这项工作中，我们使用模拟方法来研究在存在通过排阻体积相互作用与蛋白质相互作用的拥挤剂的情况下蛋白质的稳定性。一般来说，溶液中拥挤剂的存在会增强蛋白质天然状态的稳定性。然而，我们发现排阻体积的影响不仅取决于拥挤占有率，还取决于拥挤剂的几何形状和大小。具体而言，我们发现聚合物拥挤剂比球形拥挤剂具有更强的影响，并且这种影响随着聚合物长度的增加而增强，而随着球形拥挤剂尺寸的增加而减弱。这些相反的尺寸效应可以通过排阻体积减小和相分离的相互作用来解释，这两者共同决定了蛋白质折叠时拥挤剂熵的变化。
