Research Centre of Biotechnology, Russian Academy of Sciences, Moscow, 119071, Russia.
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Biochemistry (Mosc). 2023 May;88(5):610-620. doi: 10.1134/S0006297923050048.
Effects of E90K, N98S, and A149V mutations in the light chain of neurofilaments (NFL) on the structure and thermal denaturation of the NFL molecule were investigated. By using circular dichroism spectroscopy, it was shown that these mutations did not lead to the changes in α-helical structure of NFL, but they caused noticeable effects on the stability of the molecule. We also identified calorimetric domains in the NFL structure by using differential scanning calorimetry. It was shown that the E90K replacement leads to the disappearance of the low-temperature thermal transition (domain 1). The mutations cause changes in the enthalpy of NFL domains melting, as well as lead to the significant changes in the melting temperatures (T) of some calorimetric domains. Thus, despite the fact that all these mutations are associated with the development of Charcot-Marie-Tooth neuropathy, and two of them are even located very close to each other in the coil 1A, they affect differently structure and stability of the NFL molecule.
研究了神经丝轻链（NFL）中的 E90K、N98S 和 A149V 突变对 NFL 分子结构和热变性的影响。通过圆二色性光谱分析表明，这些突变并未导致 NFL 的α-螺旋结构发生变化，但它们对分子的稳定性产生了明显的影响。我们还通过差示扫描量热法鉴定了 NFL 结构中的量热域。结果表明，E90K 取代导致低温热转变（域 1）的消失。这些突变导致 NFL 域熔融焓的变化，并且导致一些量热域的熔融温度（T）发生显著变化。因此，尽管所有这些突变都与 Charcot-Marie-Tooth 神经病的发展有关，其中两个突变甚至在 coil 1A 中彼此非常接近，但它们对 NFL 分子的结构和稳定性的影响不同。
