Protein folding requires crowd control in a simulated cell.
Protein folding requires crowd control in a simulated cell.
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DOI：
10.1016/j.jmb.2010.01.074
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发表时间：
2010-04-16
影响因子：
5.6
通讯作者：
Sternberg MJ
中科院分区：
文献类型：
--
作者：
Jefferys BR;Kelley LA;Sternberg MJ
大分子拥挤对细胞内的生化过程具有深远的影响。我们使用粗粒度蛋白质模型，通过计算研究了模拟细胞中 12 个小结构域的拥挤对蛋白质折叠的影响，该模型基于朗之万动力学，旨在统一蛋白质折叠模拟和结构预测中经常不相交的目标。该模型可以预测天然构象，其准确度可与当前最好的无模板模型相媲美。它的速度足够快，能够比以前尝试进行更广泛的拥挤分析，研究多种拥挤水平的多种蛋白质，并进一步随机重复设计，以更接近构象的整体。我们发现，当拥挤接近 40% 排除体积（细胞中发现的最大水平）时，蛋白质会折叠成较少的天然状态。值得注意的是，当拥挤程度超过这个水平时，蛋白质折叠会突然失败：蛋白质更快地固定在结构上并被困在延伸的构象中。这些结果表明，小蛋白质结构域在没有伴侣的帮助下折叠的能力可能是限制细胞中大分子拥挤程度的重要因素。在这里，我们讨论了蛋白质表达水平、蛋白质大小、伴侣活性和聚集之间关系的可能影响。
Macromolecular crowding has a profound effect upon biochemical processes in the cell. We have computationally studied the effect of crowding upon protein folding for 12 small domains in a simulated cell using a coarse-grained protein model, which is based upon Langevin dynamics, designed to unify the often disjoint goals of protein folding simulation and structure prediction. The model can make predictions of native conformation with accuracy comparable with that of the best current template-free models. It is fast enough to enable a more extensive analysis of crowding than previously attempted, studying several proteins at many crowding levels and further random repetitions designed to more closely approximate the ensemble of conformations. We found that when crowding approaches 40% excluded volume, the maximum level found in the cell, proteins fold to fewer native-like states. Notably, when crowding is increased beyond this level, there is a sudden failure of protein folding: proteins fix upon a structure more quickly and become trapped in extended conformations. These results suggest that the ability of small protein domains to fold without the help of chaperones may be an important factor in limiting the degree of macromolecular crowding in the cell. Here, we discuss the possible implications regarding the relationship between protein expression level, protein size, chaperone activity and aggregation.
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DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
2.9
作者：
Das, Rhiju;Bin Qian;Baker, David
通讯作者：
Baker, David
DOI：
10.1073/pnas.0811363106
发表时间：
2009-03-10
影响因子：
11.1
作者：
DeBartolo, Joe;Colubri, Andres;Sosnick, Tobin R.
通讯作者：
Sosnick, Tobin R.
DOI：
10.1073/pnas.0408885102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Liwo, A;Khalili, M;Scheraga, HA
通讯作者：
Scheraga, HA
影响因子：
5.6
作者：
Jones, DT
通讯作者：
Jones, DT