Fig. 7.

Proposed assembly mechanism of lamin by the A11 and eA22 interactions. a Coiled-coil dimer model of full-length lamin based on the lamin 300 fragment structure. The C-terminal region of coil 2 (residues 313–386; PDB code: 1 × 8Y²⁶) and the Ig-like domain (residues 428–549; PDB code: 1IVT²⁵) of human lamin A/C, were added to the structure described in this study. For the N-terminal region of coil 2, the corresponding vimentin fragment (PDB code 3TRT;⁴² corresponding to residues 241–310 in lamin A/C) was used. The missing part (residues 283–385) in the central rod domain was built with the typical coiled-coil structure with a rise per residue of 1.5 Å. The unstructured regions (N-terminal head, NLS, and C-terminal tail) are indicated by dotted lines. Schematic drawings of the dimer model of the 54-nm-long full-length lamin A/C is in the box. b Two different tetrameric assemblies by the A11 or eA22 interactions. Each band in the same colour code as in Fig. 1a represents the coiled-coil dimer. Left, the A11 interaction-based tetrameric assembly. Right, the eA22 interaction-based tetrameric assembly. The nearby residues mapped by the disulfide or the chemical cross-linking assays are labelled. c The model of the mature lamin filament, formed by the successive and alternative A11 and eA22 interactions between the dimers. When a pair of Ig-like domains (violet square) are placed on the both sides of the tetramers, the distance between the neighbouring Ig-like domains is ~20 nm. Schematic cross-sections (a–c) of the lamin filament model are shown in the bottom (circles represent intersection of an α-helix, binding motif are in brown). The cross-section a is equivalent to Fig. 6d, and b to Fig. 6e, while c is an arbitrary arrangement of 6 α-helices