Goyal Megha, Chaudhuri Tapan K, Kuwajima Kunihiro
Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi, 444-8787, Japan; School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.
PLoS One. 2014 Dec 30;9(12):e115877. doi: 10.1371/journal.pone.0115877. eCollection 2014.
Thermal denaturation of Escherichia coli maltodextrin glucosidase was studied by differential scanning calorimetry, circular dichroism (230 nm), and UV-absorption measurements (340 nm), which were respectively used to monitor heat absorption, conformational unfolding, and the production of solution turbidity. The denaturation was irreversible, and the thermal transition recorded at scan rates of 0.5-1.5 K/min was significantly scan-rate dependent, indicating that the thermal denaturation was kinetically controlled. The absence of a protein-concentration effect on the thermal transition indicated that the denaturation was rate-limited by a mono-molecular process. From the analysis of the calorimetric thermograms, a one-step irreversible model well represented the thermal denaturation of the protein. The calorimetrically observed thermal transitions showed excellent coincidence with the turbidity transitions monitored by UV-absorption as well as with the unfolding transitions monitored by circular dichroism. The thermal denaturation of the protein was thus rate-limited by conformational unfolding, which was followed by a rapid irreversible formation of aggregates that produced the solution turbidity. It is thus important to note that the absence of the protein-concentration effect on the irreversible thermal denaturation does not necessarily means the absence of protein aggregation itself. The turbidity measurements together with differential scanning calorimetry in the irreversible thermal denaturation of the protein provided a very effective approach for understanding the mechanisms of the irreversible denaturation. The Arrhenius-equation parameters obtained from analysis of the thermal denaturation were compared with those of other proteins that have been reported to show the one-step irreversible thermal denaturation. Maltodextrin glucosidase had sufficiently high kinetic stability with a half-life of 68 days at a physiological temperature (37°C).
通过差示扫描量热法、圆二色性(230nm)和紫外吸收测量(340nm)研究了大肠杆菌麦芽糖糊精葡萄糖苷酶的热变性,这些方法分别用于监测热吸收、构象展开和溶液浊度的产生。变性是不可逆的,在0.5-1.5K/min的扫描速率下记录的热转变明显依赖于扫描速率,表明热变性受动力学控制。热转变不存在蛋白质浓度效应,表明变性受单分子过程的速率限制。通过对量热热谱图的分析,一步不可逆模型很好地描述了该蛋白质的热变性。量热法观察到的热转变与紫外吸收监测的浊度转变以及圆二色性监测的展开转变表现出极好的一致性。因此,该蛋白质的热变性受构象展开的速率限制,随后是聚集体的快速不可逆形成,从而产生溶液浊度。因此,重要的是要注意,不可逆热变性不存在蛋白质浓度效应并不一定意味着不存在蛋白质聚集本身。在蛋白质的不可逆热变性中,浊度测量与差示扫描量热法相结合,为理解不可逆变性的机制提供了一种非常有效的方法。将热变性分析得到的阿伦尼乌斯方程参数与其他已报道表现出一步不可逆热变性的蛋白质的参数进行了比较。麦芽糖糊精葡萄糖苷酶具有足够高的动力学稳定性,在生理温度(37°C)下的半衰期为68天。