Abstract
The nuclear lamins form a two-dimensional matrix that provides integrity to the cell nucleus and participates in nuclear activities. Mutations in the region of human LMNA encoding the carboxyl-terminal tail Lamin A/C are associated with forms of muscular dystrophy and familial partial lipodystrophy (FPLD). To help discriminate tissue-specific phenotypes, we have solved at 1.4-Å resolution the three-dimensional crystal structure of the lamin A/C globular tail. The domain adopts a novel, all β immunoglobulin-like fold. FPLD-associated mutations cluster within a small surface, whereas muscular dystrophy-associated mutations are distributed throughout the protein core and on its surface. These findings distinguish myopathy- and lipodystrophy-associated mutations and provide a structural framework for further testing hypotheses concerning lamin function.
Original language | English (US) |
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Pages (from-to) | 17381-17384 |
Number of pages | 4 |
Journal | Journal of Biological Chemistry |
Volume | 277 |
Issue number | 20 |
DOIs | |
State | Published - May 17 2002 |
Externally published | Yes |