Breydo Leonid, Reddy Krishna D, Piai Alessandro, Felli Isabella C, Pierattelli Roberta, Uversky Vladimir N
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Biochim Biophys Acta. 2014 Feb;1844(2):346-57. doi: 10.1016/j.bbapap.2013.11.004. Epub 2013 Nov 16.
The intracellular environment contains high concentrations of macromolecules occupying up to 30% of the total cellular volume. Presence of these macromolecules decreases the effective volume available for the proteins in the cell and thus increases the effective protein concentrations and stabilizes the compact protein conformations. Macromolecular crowding created by various macromolecules such as proteins, nucleic acids, and carbohydrates has been shown to have a significant effect on a variety of cellular processes including protein aggregation. Most studies of macromolecular crowding have used neutral, flexible polysaccharides that function primarily via excluded volume effect as model crowding agents. Here we have examined the effects of more rigid polysaccharides on protein structure and aggregation. Our results indicate that rigid and flexible polysaccharides influence protein aggregation via different mechanisms and suggest that, in addition to excluded volume effect, changes in solution viscosity and non-specific protein-polymer interactions influence the structure and dynamics of proteins in crowded environments.
细胞内环境含有高浓度的大分子，其占据了高达细胞总体积的30%。这些大分子的存在减少了细胞内蛋白质可利用的有效体积，从而提高了有效蛋白质浓度，并稳定了紧密的蛋白质构象。由蛋白质、核酸和碳水化合物等各种大分子造成的大分子拥挤现象已被证明对包括蛋白质聚集在内的多种细胞过程有显著影响。大多数关于大分子拥挤的研究使用主要通过排阻体积效应起作用的中性、柔性多糖作为模型拥挤剂。在这里，我们研究了更刚性的多糖对蛋白质结构和聚集的影响。我们的结果表明，刚性和柔性多糖通过不同机制影响蛋白质聚集，并表明除了排阻体积效应外，溶液粘度的变化和非特异性蛋白质-聚合物相互作用会影响拥挤环境中蛋白质的结构和动力学。
