Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University, 79104 Freiburg, Germany. Electronic address: https://twitter.com/@_posti.
Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University, 79104 Freiburg, Germany. Electronic address: https://twitter.com/@BenjaminLickert.
J Mol Biol. 2022 Sep 15;434(17):167679. doi: 10.1016/j.jmb.2022.167679. Epub 2022 Jun 8.
Allosteric communication between distant protein sites represents a key mechanism of biomolecular regulation and signal transduction. Compared to other processes such as protein folding, however, the dynamical evolution of allosteric transitions is still not well understood. As an example of allosteric coupling between distant protein regions, we consider the global open-closed motion of the two domains of T4 lysozyme, which is triggered by local motion in the hinge region. Combining extensive molecular dynamics simulations with a correlation analysis of interresidue contacts, we identify a network of interresidue distances that move in a concerted manner. The cooperative process originates from a cogwheel-like motion of the hydrophobic core in the hinge region, which constitutes an evolutionary conserved and flexible transmission network. Through rigid contacts and the protein backbone, the small local changes of the hydrophobic core are passed on to the distant terminal domains and lead to the emergence of a rare global conformational transition. As in an Ising-type model, the cooperativity of the allosteric transition can be explained via the interaction of local fluctuations.
蛋白质上远距离的构象变化之间的变构通讯是生物分子调控和信号转导的关键机制。然而，与蛋白质折叠等其他过程相比，变构转变的动力学演变仍然不太清楚。作为蛋白质远距离区域之间变构偶联的一个例子，我们考虑 T4 溶菌酶两个结构域的整体开闭运动，该运动由铰链区的局部运动触发。我们将广泛的分子动力学模拟与残基间相互作用的相关分析相结合，确定了一个残基间距离协同移动的网络。协同过程源于铰链区疏水区的齿轮状运动，它构成了一个进化保守且灵活的传递网络。通过刚性接触和蛋白质骨架，疏水区的微小局部变化传递到遥远的末端结构域，导致罕见的全局构象转变的出现。就像伊辛型模型一样，变构转变的协同性可以通过局部波动的相互作用来解释。
