title: The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy.
abstract: 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.
authors.affiliation: Département d'Ingénierie et d'Etudes des Protéines, CEA Saclay, 91191, Gif-sur-Yvette, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Krimm
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ostlund
authors.forename: Bernard
authors.initials: B
authors.lastname: Gilquin
authors.forename: Joël
authors.initials: J
authors.lastname: Couprie
authors.forename: Paul
authors.initials: P
authors.lastname: Hossenlopp
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mornon
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Courvalin
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Worman
authors.forename: Sophie
authors.initials: S
authors.lastname: Zinn-Justin
mesh_terms: D000595:Amino Acid Sequence; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism; D002942:Circular Dichroism; D017124:Conserved Sequence; D007136:Immunoglobulins / Q000235:genetics; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D008060:Lipodystrophy / Q000235:genetics* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D007136:Immunoglobulins; D034904:Lamin Type A