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

Biochem Biophys Res Commun. 2021 Apr 23:550:191-196. doi: 10.1016/j.bbrc.2021.02.102. Epub 2021 Mar 9.


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 lamin-related diseases at the molecular level.

Keywords: Crystal structure; Dimeric assembly; Ig-like domain; Lamin A/C; Lamin B1; Lamin filament.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Immunoglobulin Domains*
  • Lamin Type A / chemistry*
  • Lamin Type A / metabolism*
  • Lamin Type B / chemistry*
  • Lamin Type B / metabolism*
  • Models, Molecular
  • Protein Multimerization*
  • Protein Stability


  • Lamin Type A
  • Lamin Type B