Homouz Dirar, Perham Michael, Samiotakis Antonios, Cheung Margaret S, Wittung-Stafshede Pernilla
Department of Physics, University of Houston, Houston, TX 77204, USA.
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11754-9. doi: 10.1073/pnas.0803672105. Epub 2008 Aug 12.
How the crowded environment inside cells affects the structures of proteins with aspherical shapes is a vital question because many proteins and protein-protein complexes in vivo adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e., Borrelia burgdorferi VlsE) in crowded, cell-like conditions. The results show that macromolecular crowding affects protein-folding dynamics as well as overall protein shape. In crowded milieus, distinct conformational changes in VlsE are accompanied by secondary structure alterations that lead to exposure of a hidden antigenic region. Our work demonstrates the malleability of "native" proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo.
细胞内的拥挤环境如何影响非球形蛋白质的结构是一个至关重要的问题，因为体内许多蛋白质和蛋白质 - 蛋白质复合物都呈现各向异性的形状。在这里，我们通过在拥挤的、类似细胞的条件下对一种足球形状的蛋白质（即伯氏疏螺旋体VlsE）进行计算和实验研究来解决这个问题。结果表明，大分子拥挤会影响蛋白质折叠动力学以及蛋白质的整体形状。在拥挤的环境中，VlsE中明显的构象变化伴随着二级结构的改变，从而导致一个隐藏的抗原区域暴露。我们的工作证明了“天然”蛋白质的可塑性，并暗示拥挤诱导的形状变化可能对体内蛋白质的功能及功能失调具有重要意义。
