Beta-strand-mediated dimeric formation of the Ig-like domains of human lamin A/C and B1

Lamins are nuclear intermediate filament proteins that play an essential role in maintaining the nuclear structure by forming a 3-D meshwork. Lamins consist of the N-terminal unstructured head, the coiled coil rod domain, and the C-terminal tail, which is mostly unstructured except for the Ig-like domain. To date, the Ig-like domain has been characterized as a monomeric structure. Here, we determined the crystal structures of human lamin A/C, including the Ig-like domain and its N-and C-terminal flanking sequences. Interestingly, the structures showed a homodimer formed by beta-strand interactions between the N-and C-terminal flanking sequences. This interaction also provides a molecular implication for the creation of a 3-D meshwork between the 3.5-nm-thick filaments. Furthermore, we determined the crystal structure of the corresponding region of lamin B1. The structure showed a similar dimeric assembly, also formed by beta-strand interactions, albeit the intersubunit distance was much shorter. Since the Ig-like domain contains many genetic hotspots causing lamin-related diseases in lamin A/C, our findings will help understand the detailed assembly of lamins in a 3-D meshwork structure and laminrelated diseases at the molecular level. (c) 2021 Published by Elsevier Inc.

Automated summary

The study revealed the crystal structures of human lamin A/C and lamin B1, showing their existence as homodimers and contributing to the understanding of lamin assembly in a 3D meshwork structure. Notably, the presence of genetic hotspots in the Ig-like domain of lamin A/C, which may be associated with lamin-related diseases, was highlighted.