Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
J Am Chem Soc. 2011 May 11;133(18):7116-20. doi: 10.1021/ja200067p. Epub 2011 Apr 20.
Thirty percent of a cell's volume is filled with macromolecules, and protein chemistry in a crowded environment is predicted to differ from that in dilute solution. We quantified the effect of crowding by globular proteins on the equilibrium thermodynamic stability of a small globular protein. Theory has long predicted that crowding should stabilize proteins, and experiments using synthetic polymers as crowders show such stabilizing effects. We find that protein crowders can be mildly destabilizing. The destabilization arises from a competition between stabilizing excluded-volume effects and destabilizing nonspecific interactions, including electrostatic interactions. This competition results in tunable stability, which could impact our understanding of the spatial and temporal roles of proteins in living systems.
细胞体积的 30%被大分子填满，在拥挤的环境中，蛋白质化学预计会与在稀溶液中的有所不同。我们通过球状蛋白定量了拥挤效应对小球状蛋白平衡热力学稳定性的影响。理论很早就预测了拥挤应该稳定蛋白质，并且使用合成聚合物作为拥挤物的实验显示了这种稳定作用。我们发现蛋白质拥挤剂可能会轻微地使蛋白质不稳定。这种不稳定性源于稳定的排斥体积效应和不稳定的非特异性相互作用（包括静电相互作用）之间的竞争。这种竞争导致了可调节的稳定性，这可能会影响我们对蛋白质在生命系统中的空间和时间作用的理解。
