Filament assembly of the lamin in the absence of helix 1A.

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.