Biophysics Graduate Group, California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720-3220, USA.
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3796-801. doi: 10.1073/pnas.1115519109. Epub 2012 Feb 21.
Recently, the role of force in cellular processes has become more evident, and now with advances in force spectroscopy, the response of proteins to force can be directly studied. Such studies have found that native proteins are brittle, and thus not very deformable. Here, we examine the mechanical properties of a class of intermediates referred to as the molten globule state. Using optical trap force spectroscopy, we investigated the response to force of the native and molten globule states of apomyoglobin along different pulling axes. Unlike natively folded proteins, the molten globule state of apomyoglobin is compliant (large distance to the transition state); this large compliance means that the molten globule is more deformable and the unfolding rate is more sensitive to force (the application of force or tension will have a more dramatic effect on the unfolding rate). Our studies suggest that these are general properties of molten globules and could have important implications for mechanical processes in the cell.
最近,力在细胞过程中的作用变得更加明显,现在随着力谱学的进步,可以直接研究蛋白质对力的响应。这些研究发现,天然蛋白质是脆性的,因此不太可变形。在这里,我们研究了一类中间状态,即所谓的无规卷曲状态的力学性质。使用光阱力谱法,我们沿着不同的拉伸轴研究了去折叠肌红蛋白的天然状态和无规卷曲状态对力的响应。与天然折叠的蛋白质不同,去折叠肌红蛋白的无规卷曲状态是顺应性的(离过渡状态的距离较大);这种大的顺应性意味着无规卷曲状态更具可变形性,并且解折叠速率对力更敏感(施加力或张力会对解折叠速率产生更显著的影响)。我们的研究表明,这些是无规卷曲状态的普遍性质,这可能对细胞中的力学过程具有重要意义。