Computational Science Program, University of Texas at El Paso, El Paso, TX 79902, USA.
Department of Physics, University of Texas at El Paso, El Paso, TX 79902, USA.
Cells. 2023 Jan 5;12(2):238. doi: 10.3390/cells12020238.
Microtubules are key players in several stages of the cell cycle and are also involved in the transportation of cellular organelles. Microtubules are polymerized by α/β tubulin dimers with a highly dynamic feature, especially at the plus ends of the microtubules. Therefore, understanding the interactions among tubulins is crucial for characterizing microtubule dynamics. Studying microtubule dynamics can help researchers make advances in the treatment of neurodegenerative diseases and cancer. In this study, we utilize a series of computational approaches to study the electrostatic interactions at the binding interfaces of tubulin monomers. Our study revealed that among all the four types of tubulin-tubulin binding modes, the electrostatic attractive interactions in the α/β tubulin binding are the strongest while the interactions of α/α tubulin binding in the longitudinal direction are the weakest. Our calculations explained that due to the electrostatic interactions, the tubulins always preferred to form α/β tubulin dimers. The interactions between two protofilaments are the weakest. Thus, the protofilaments are easily separated from each other. Furthermore, the important residues involved in the salt bridges at the binding interfaces of the tubulins are identified, which illustrates the details of the interactions in the microtubule. This study elucidates some mechanistic details of microtubule dynamics and also identifies important residues at the binding interfaces as potential drug targets for the inhibition of cancer cells.
微管是细胞周期几个阶段的关键参与者，也参与细胞细胞器的运输。微管由α/β微管二聚体聚合而成，具有高度动态的特征，特别是在微管的正极末端。因此，了解微管中 tubulin 之间的相互作用对于表征微管动力学至关重要。研究微管动力学可以帮助研究人员在治疗神经退行性疾病和癌症方面取得进展。在这项研究中，我们利用一系列计算方法研究了微管单体结合界面的静电相互作用。我们的研究表明，在所有四种类型的 tubulin-tubulin 结合模式中，α/β 微管结合中的静电吸引相互作用最强，而纵向方向的α/α 微管结合相互作用最弱。我们的计算解释了由于静电相互作用，tubulin 总是优先形成 α/β 微管二聚体。两个原纤维之间的相互作用最弱。因此，原纤维很容易彼此分离。此外，还鉴定了微管结合界面处盐桥中涉及的重要残基，说明了微管中相互作用的细节。这项研究阐明了微管动力学的一些机制细节，并确定了结合界面上的重要残基作为抑制癌细胞的潜在药物靶点。
