Theoretical and Computational Biophysics, Max Planck Institute for Multidisciplinary Sciences, D-37077 Göttingen, Germany.
Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2115516119. doi: 10.1073/pnas.2115516119. Epub 2022 Mar 18.
SignificanceThe mechanochemical basis of microtubule growth, which is essential for the normal function and division of eukaryotic cells, has remained elusive and controversial, despite extensive work. In particular, recent findings have created the paradox that the microtubule plus-end tips look very similar during both growing and shrinking phases, thereby challenging the traditional textbook picture. Our large-scale atomistic simulations resolve this paradox and explain microtubule growth and shrinkage dynamics as a process governed by energy barriers between protofilament conformations, the heights of which are in turn fine-tuned by different nucleotide states, thus implementing an information-driven Brownian ratchet.
尽管已经进行了广泛的研究,但微管生长的机械化学基础对于真核细胞的正常功能和分裂仍然难以捉摸且存在争议。特别是,最近的发现产生了一个悖论,即在生长和收缩阶段,微管的正极尖端看起来非常相似,从而挑战了传统的教科书图片。我们的大规模原子模拟解决了这个悖论,并解释了微管的生长和收缩动力学是由原丝构象之间的能量势垒控制的过程,其高度又反过来被不同的核苷酸状态精细调节,从而实现了信息驱动的布朗棘轮。