PDF(Pubmed)
Abstract：
Tubulin has been recently reported to form a large family consisting of various gene isoforms; however, the differences in the molecular features of tubulin dimers composed of a combination of these isoforms remain unknown. Therefore, we attempted to elucidate the physical differences in the molecular motility of these tubulin dimers using the method of measurable pico-meter-scale molecular motility, diffracted X-ray tracking (DXT) analysis, regarding characteristic tubulin dimers, including neuronal TUBB3 and ubiquitous TUBB5. We first conducted a DXT analysis of neuronal (TUBB3-TUBA1A) and ubiquitous (TUBB5-TUBA1B) tubulin dimers and found that the molecular motility around the vertical axis of the neuronal tubulin dimer was lower than that of the ubiquitous tubulin dimer. The results of molecular dynamics (MD) simulation suggest that the difference in motility between the neuronal and ubiquitous tubulin dimers was probably caused by a change in the major contact of Gln245 in the T7 loop of TUBB from Glu11 in TUBA to Val353 in TUBB. The present study is the first report of a novel phenomenon in which the pico-meter-scale molecular motility between neuronal and ubiquitous tubulin dimers is different.
摘要：
最近有报道称，微管蛋白形成了一个由各种基因亚型组成的大家庭；然而，由这些同工型组合组成的微管蛋白二聚体的分子特征差异仍然未知。因此,我们试图阐明这些微管蛋白二聚体的分子运动性的物理差异，使用可测量的皮米尺度的分子运动性的方法，衍射X射线跟踪（DXT）分析，关于特征性微管蛋白二聚体，包括神经元TUBB3和普遍存在的TUBB5。我们首先对神经元（TUBB3-TUBA1A）和普遍存在的（TUBB5-TUBA1B）微管蛋白二聚体进行了DXT分析，发现神经元微管蛋白二聚体绕垂直轴的分子运动性低于普遍存在的微管蛋白二聚体。分子动力学（MD）模拟的结果表明，神经元和普遍存在的微管蛋白二聚体之间的运动性差异可能是由于TUBB的T7环中Gln245的主要接触从TUBA中的Glu11到TUBB中的Val353的变化引起的。本研究是一种新现象的首次报道，其中神经元和普遍存在的微管蛋白二聚体之间的皮米尺度分子运动性不同。
