Structure of the lamin A/C R482W mutant responsible for dominant familial partial lipodystrophy (FPLD)

Journal Article · Fri Aug 07 04:00:00 EDT 2009 · Acta Crystallogr. F

DOI:https://doi.org/10.1107/S1744309109020302· OSTI ID:1005769

Magracheva, Eugenia; Kozlov, Serguei; Stewart, Colin L; Wlodawer, Alexander; Zdanov, Alexander

Proteins of the A-type lamin family, which consists of two members, lamin A and lamin C, are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A-type lamins have recently become the focus of extensive functional studies as a consequence of the linking of at least eight congenital diseases to mutations in the lamin A/C gene (LMNA). This spectrum of pathologies, which mostly manifest themselves as dominant traits, includes muscle dystrophies, dilated cardiomyopathies, the premature aging syndrome Hutchinson-Guilford progeria and familial partial lipodystrophy (FPLD). The crystal structure of the lamin A/C mutant R482W, a variant that causes FPLD, has been determined at 1.5 {angstrom} resolution. A completely novel aggregation state of the C-terminal globular domain and the position of the mutated amino-acid residue suggest means by which the mutation may affect lamin A/C-protein and protein-DNA interactions.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005769
• Journal Information: Acta Crystallogr. F, Journal Name: Acta Crystallogr. F Journal Issue: (7) ; 07, 2009 Vol. 65; ISSN 1744-3091
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
AGING
CONGENITAL DISEASES
CRYSTAL STRUCTURE
FUNCTIONALS
GENES
MUSCLES
MUTANTS
MUTATIONS
PROTEINS
RESIDUES
RESOLUTION