Open AccessStructure of the lamin A/C R482W mutant responsible for dominant familial partial lipodystrophy (FPLD)
Author(s) -
Magracheva Eugenia,
Kozlov Serguei,
Stewart Colin L.,
Wlodawer Alexander,
Zdanov Alexander
Publication year - 2009
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309109020302
Subject(s) - lamin , lmna , nuclear lamina , biology , genetics , mutant , mutation , gene , nuclear protein , transcription factor
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 Å 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.