Structure of the globular tail of nuclear lamin.
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-A resolution the three-dimensional crystal structure of the lamin A/C globular tail. The domain adopts a novel, all beta 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.
Dhe-Paganon
Sirano
S
Joslin Diabetes Center & Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Werner
Eric D
ED
Chi
Young-In
YI
Shoelson
Steven E
SE
D000595:Amino Acid Sequence; D000818:Animals; D000845:Annelida; D001001:Anura; D018360:Crystallography, X-Ray; D004175:Diptera; D005399:Fishes; D006801:Humans; D034904:Lamin Type A; D034882:Lamins; D008060:Lipodystrophy / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins