The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy

Structure. 2002 Jun;10(6):811-23. doi: 10.1016/s0969-2126(02)00777-3.


Lamins are nuclear intermediate filaments that, together with lamin-associated proteins, maintain nuclear shape and provide a structural support for chromosomes and replicating DNA. We have determined the solution structure of the human lamin A/C C-terminal globular domain which contains specific mutations causing four different heritable diseases. This domain encompasses residues 430-545 and adopts an Ig-like fold of type s. We have also characterized by NMR and circular dichroism the structure and thermostability of three mutants, R453W and R482W/Q, corresponding to "hot spots" causing Emery-Dreifuss muscular dystrophy and Dunnigan-type lipodystrophy, respectively. Our structure determination and mutant analyses clearly show that the consequences of the mutations causing muscle-specific diseases or lipodystrophy are different at the molecular level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Circular Dichroism
  • Conserved Sequence
  • Immunoglobulins / genetics
  • Lamin Type A / genetics*
  • Lamin Type A / metabolism
  • Lipodystrophy / genetics*
  • Lipodystrophy / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / metabolism
  • Mutation
  • Phenotype
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Analysis, Protein


  • Immunoglobulins
  • Lamin Type A