title: Structure of the globular tail of nuclear lamin.
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-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.
authors.affiliation: Joslin Diabetes Center & Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Sirano
authors.initials: S
authors.lastname: Dhe-Paganon
authors.forename: Eric D
authors.initials: ED
authors.lastname: Werner
authors.forename: Young-In
authors.initials: YI
authors.lastname: Chi
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shoelson
mesh_terms: 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
chemical_list: D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins