Department of Biochemistry, University of Zurich, Zurich, Switzerland.
Nucleus. 2022 Dec;13(1):49-57. doi: 10.1080/19491034.2022.2032917.
Lamins are the major constituent of the nuclear lamina, a protein meshwork underlying the inner nuclear membrane. Nuclear lamins are type V intermediate filaments that assemble into ~3.5 nm thick filaments. To date, only the conditions for the assembly of lamin (-lamin) are known. Here, we investigated the assembly of -lamin filaments by cryo-electron microscopy and tomography. We show that -lamin is composed of ~3.5 nm protofilaments that further interact and are often seen as 6-8 nm thick filaments. We show that the assembly of lamin filaments is undisturbed by the removal of flexible domains, the intrinsically unstructured head and tail domains. In contrast, much of the coiled-coil domains are scaffold elements that are essential for filament assembly. Moreover, our results suggest that -lamin helix 1A has a minor scaffolding role but is important to the lateral assembly regulation of lamin protofilaments.
核纤层蛋白是核纤层的主要成分，核纤层是位于内核膜下的蛋白质网格。核纤层蛋白是一种 V 型中间丝，组装成约 3.5nm 厚的丝。迄今为止，仅已知组装 lamin（-lamin）的条件。在这里，我们通过冷冻电子显微镜和断层扫描研究了-lamin 丝的组装。我们表明，-lamin 由约 3.5nm 的原纤维组成，这些原纤维进一步相互作用，通常被视为 6-8nm 厚的纤维。我们表明，lamin 丝的组装不受去除柔性结构域、无规卷曲结构域的头和尾结构域的影响。相比之下，大部分卷曲螺旋结构域是支架元件，对于纤维组装是必不可少的。此外，我们的结果表明，-lamin 螺旋 1A 具有较小的支架作用，但对 lamin 原纤维的侧向组装调节很重要。
